TY - JOUR. T1 - Genetic polymorphisms in host innate immune sensor genes and the risk of nasopharyngeal carcinoma in North Africa. AU - Moumad, K.. AU - Lascorz, J.. AU - Bevier, M.. AU - Khyatti, M.. AU - Ennaji, M.M.. AU - Benider, A.. AU - Huhn, S.. AU - Lu, S.. AU - Chouchane, L.. AU - Corbex, M.. AU - Hemminki, K.. AU - Forsti, A.. N1 - ITG-H10B; DPH; U-MRH; JIF; DOI; PDF; E-only; Abstract; DSPACE56. PY - 2013. Y1 - 2013. N2 - Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world. It is an Epstein-Barr virus-associated malignancy with an unusual racial and geographical distribution. The host innate immune sensor genes play an important role in infection recognition and immune response against viruses. Therefore, we examined the association between polymorphisms in genes within a group of pattern recognition receptors (including families of toll-like receptors, C-type lectin receptors, and RIG-I-like receptors) and NPC susceptibility. Twenty six single nucleotide ...
IG-I is a major innate immune sensor for viral infection, triggering an interferon-mediated antiviral response upon cytosolic detection of viral RNA. Double-strandedness and 5-terminal triphosphates were identified as motifs required to elicit optimal immunological signaling. However, very little is known about the response dynamics of the RIG-I pathway, which is crucial for the cells ability to react to diverse classes of viral RNA, while maintaining self-tolerance. In the present study, we addressed the molecular mechanism of RIG-I signal detection and its translation into pathway activation. By employing highly quantitative methods, we could establish the length of the double-stranded RNA (dsRNA) to be the most critical determinant of response strength. Size exclusion chromatography and direct visualization in scanning force microscopy suggested, that this was due to cooperative oligomerization of RIG-I along dsRNA. Initiation efficiency of this oligomerization process was critically ...
Route of Infection Determines the Impact of Type I Interferons on Innate Immunity to Listeria monocytogenes. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The innate immune system plays a critical role in both the initial response to an invading pathogen, which frequently limits or contains pathogen replication and dissemination, and the induction of an effective adaptive immune response, which is most often the primary mechanism for pathogen clearance. The characteristics of the innate immune response are determined in part by the pathogen initiating the response but can also be influenced by the type of cell in which the response is generated. In this report, we examined the functional PRR-mediated pathways present in human neuronal cells and differentiated primary rat neurons, with a particular focus on those pathways previously identified as being important for antiviral innate immune responses in other cell types. We drew four main conclusions. First, human neuronal cells possess functional TLR3-, TLR4-, RIG-I-, and MDA5-mediated PRR pathways whose activity was maturation-dependent. Second, both extracellular and transfected poly(I-C) induced ...
Detection of pathogens by all living organisms is the primary step needed to implement a coherent and efficient immune response. This implies a mediation by different soluble and/or membrane-anchored proteins related to innate immune receptors called PRRs (pattern recognition receptors) to trigger immune signaling pathways. In most invertebrates, their roles have been inferred by analogy to those already characterized in vertebrate homologues. Despite the induction of their gene expression upon challenge and the presence of structural domains associated with the detection of pathogen-associated molecular patterns (PAMPs) in their sequence, their exact role in the induction of immune response and their binding capacity still remain to be demonstrated. To this purpose, we developed a fast interactome approach, usable on any host-pathogen couple, to identify soluble proteins capable of directly or indirectly detecting the presence of pathogens. To investigate the molecular basis of immune recognition
TY - JOUR. T1 - An essential role of macrophage inflammatory protein 1α/CCL3 on the expression of hosts innate immunities against infectious complications. AU - Takahashi, Hitoshi. AU - Tashiro, Tsuguhiko. AU - Miyazaki, Masaru. AU - Kobayashi, Makiko. AU - Pollard, Richard B.. AU - Suzuki, Fujio. PY - 2002/12/1. Y1 - 2002/12/1. N2 - Sepsis was induced by well-controlled cecal ligation and puncture (CLP) in macrophage inflammatory protein 1α (MIP-1α)/CCL3 knock-out (CCL3-/-) and severe combined immunodeficiency (SCID) mice. CCL3-/- mice and their littermates (CCL3+/+ mice) treated with anti-CCL3 monoclonal antibodies were susceptible (0-20% survival) to CLP-induced sepsis, and CCL3-/- mice supplemented with recombinant (r)CCL3 (250 ng/mouse) and CCL3+/+ mice were resistant (70-80% survival). The resistance of SCID mice to CLP was markedly improved by the rCCL3 administration (88% survival), and SCID mice treated with saline were shown to be middling resistant to the same CLP (45% survival). ...
Herpes simplex virus type 1 (HSV-1) infection triggers a rapid induction of host innate immune responses. The type I interferon (IFN) signal pathway is a central aspect of host defense which induces a wide range of antiviral proteins to control infection of incoming pathogens. In some cases, viral invasion also induces DNA damage response, autophagy, endoplasmic reticulum stress, cytoplasmic stress granules and other innate immune responses, which in turn affect viral infection. However, HSV-1 has evolved multiple strategies to evade host innate responses and facilitate its infection. In this review, we summarize the most recent findings on the molecular mechanisms utilized by HSV-1 to counteract host antiviral innate immune responses with specific focus on the type I IFN signal pathway.
The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-beta (IFN-beta). IFI16 directly associated with IFN-beta-inducing viral DNA motifs. STING, a critical mediator of IFN-beta responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-kappa B induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-beta induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call AIM2-like receptors (ALRs ...
Innate immunity is the inborn immunity of the person. Innate immunity is non-specific in nature. The response of innate immune depends on the recognition o..
Patterns of selection acting on immune defence genes have recently been the focus of considerable interest. Yet, when it comes to vertebrates, studies have mainly focused on the acquired branch of the immune system. Consequently, the direction and strength of selection acting on genes of the vertebrate innate immune defence remain poorly understood. Here, we present a molecular analysis of selection on an important receptor of the innate immune system of vertebrates, the Toll-like receptor 2 (TLR2), across 17 rodent species. Although purifying selection was the prevalent evolutionary force acting on most parts of the rodent TLR2, we found that codons in close proximity to pathogen- binding and TLR2-TLR1 heterodimerization sites have been subject to positive selection. This indicates that parasite-mediated selection is not restricted to acquired immune system genes like the major histocompatibility complex, but also affects innate defence genes. To obtain a comprehensive understanding of ...
TY - JOUR. T1 - NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. AU - Lahaye, Xavier. AU - Gentili, Matteo. AU - Silvin, Aymeric. AU - Conrad, Cécile. AU - Picard, Léa. AU - Jouve, Mabel. AU - Zueva, Elina. AU - Maurin, Mathieu. AU - Nadalin, Francesca. AU - Knott, Gavin J.. AU - Zhao, Baoyu. AU - Du, Fenglei. AU - Rio, Marlène. AU - Amiel, Jeanne. AU - Fox, Archa H.. AU - Li, Pingwei. AU - Etienne, Lucie. AU - Bond, Charles S.. AU - Colleaux, Laurence. AU - Manel, Nicolas. PY - 2018/10/4. Y1 - 2018/10/4. N2 - Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an ...
RIG-I is a cytoplasmic surveillance protein that contributes to the earliest stages of the vertebrate innate immune response. The protein specifically recognizes 5-triphosphorylated RNA structures that are released into the cell by viruses, such as influenza and hepatitis C. To understand the energ …
In this study, we aimed to define the established associations between MHC genes and viral outcomes in the context of the IFNL3-linked polymorphisms. We were in a unique position to address this, as we were able to investigate these relationships in a cohort of women who had been infected with HCV from a single source. We wished to address whether the observed MHC associations would remain significant in the context of the profound innate immune effect.. We first considered whether there might be a differential effect according to the characteristics of the innate immune response, by analysing the impact of carriage of either the protective or deleterious IFNL3 genotype with respect to the HLA effect on viral outcomes. In our HLA Class I analysis, we did, to an extent, observe this effect. The presence of the protective alleles HLA-B*27 and -C*01 was significantly enriched in those with viral clearance if the unfavourable IFNL3 genotype was present. In this cohort, the HLA-B*27 and C*01 alleles ...
Lien vers Pubmed [PMID] - 21512573. Nature 2011 Apr;472(7343):361-5. TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by human immunodeficiency virus (HIV)-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm. Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice and several reports indicate that TRIM5 has a role in signal transduction, but the precise mechanism of restriction is unknown. Here we demonstrate that TRIM5 promotes innate immune signalling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13-UEV1A (also known as UBE2N-UBE2V1), TRIM5 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex and stimulate AP-1 and NFκB signalling. Interaction with the HIV-1 capsid lattice greatly enhances the UBC13-UEV1A-dependent E3 ...
My prior studies focused on the pathogenesis of cigarette-smoke (CS) -induced lung diseases such as chronic obstructive pulmonary disease (COPD), wherein we demonstrated that the IL-18 system plays an important role in the pathogenesis of CS-induced emphysematous lung destruction. These studies led me to question the effect of CS on innate immunity on the interaction between the host and microorganisms and, for this purpose, I had established a murine cigarette smoke and virus co-exposure model. These studies revealed important insight into the interaction between CS and the innate immunity resulting in a publication in the Journal of Clinical Investigation. In that study, we identified that CS smoke selectively augments respiratory antiviral innate immune responses via a MAVS-RLHs antiviral signaling pathway. To gain better understanding of the mechanisms, my laboratory is focusing on the role(s) of mitochondrial dysfunction and immune dysregulation in the setting of smoking exposure. By ...
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Oral manifestations of HIV have been documented since the initial presentation of the HIV/AIDS epidemic of the 80s. The most common oral complication was candi...
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Immunity System. Discuss about Immunity System, Two Divisions of Mammal Immune System, INNATE IMMUNITY (NON-SPECIFIC), ACQUIRED IMMUNITY....
Mycobacterial infection induces a specific human innate immune response John D Blischak , Ludovic Tailleux , Amy Mitrano , Luis B Barreiro , Yoav Gilad doi: http://dx.doi.org/10.1101/017483 The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune…
Innate immunity represents the foremost barrier to viral infection. In order to infect a cell efficiently, viruses need to evade innate immune effectors such as interferons and inflammatory cytokines. Pattern recognition receptors can detect viral components or pathogen-associated molecular patterns. These receptors then elicit innate immune responses that result in the generation of type I interferons and proinflammatory cytokines. Organized by the Society for General Microbiology, one session of this conference focused on the current state-of-the-art knowledge on innate barriers to infection of different RNA and DNA viruses. Experts working on innate immunity in the context of viral infection provided insight into different aspects of innate immune recognition and also discussed areas for future research. Here, we provide an overview of the session on innate barriers to infection.. ...
The innate immune system is the first line of response to pathogens and tissue injury. Specialized cells have evolved mechanisms to detect microbial and distress signals and translate these into effector mechanisms that fight infections, amplify inflammation, initiate acquired immunity and eventually resolve. Although the innate immune response is usually associated with infectious disease, it has been implicated in a broad range of diseases, including cancer, autoimmunity, degenerative and vascular diseases. This conference provides multidisciplinary perspectives on innate immunity, from fundamental science to clinical aspects of disease, as well as therapeutic approaches to immune modulation. The conference program will focus on recent advances in this rapidly developing field. Presentations will provide new insights into mechanisms of microbial and distress sensing and the effector mechanisms of innate immune cells including macrophages, neutrophils, dendritic cells and innate lymphoid cells. ...
Clipped females, with an increased heat loss rate, fed their offspring less frequently (Figs 1 and 2), and had higher innate immune function (Table 2, Fig. 3), than unclipped females. Males fed their offspring at similar rates regardless of treatment (Figs 1 and 2), and their immune function indices were unaffected by the experiment (Fig. 3). Despite reduced effort and increased investment in self-maintenance in females, body mass and size were not compromised in nestlings of clipped parents (Table S1). Thus, reduced constraints of overheating allowed for increased constitutive innate immune function, but only in females. A relatively higher level of constitutive innate immune function is supposed to be beneficial for survival. For example, levels of complement activity have been shown to correlate positively with survival (Hegemann et al., 2015), and high BKA correlated positively with survival probability upon an epidemic outbreak (Wilcoxen et al., 2010).. These benefits possibly occur because ...
Microbial DNA induces the expression of type I IFNs and proinflammatory cytokines, leading to the potent induction of innate immunity (Stetson and Medzhitov, 2006a; Kawai and Akira, 2009). Furthermore, synthesized DNA stimulates the innate immune system and acts as a good adjuvant to induce the efficient induction of acquired immune responses (Ishii et al., 2008a). Indeed, TLR9, the receptor for single-stranded DNAs containing unmethylated CpG motifs, is involved in the protection of hosts suffering DNA virus infection, and the ligands for TLR9 efficiently induce acquired immune responses upon vaccination. However, dsDNA derived from bacteria and DNA viruses, as well as host genomic DNA from dying cells, could induce the expression of both type I IFNs and IFN-inducible genes via a TLR-independent pathway (Okabe et al., 2005; Ishii et al., 2006; Stetson and Medzhitov, 2006b; Stetson et al., 2008). Although the specific sensors involved in dsDNA-induced innate immune responses are still unclear, ...
The rapid detection of microbial agents is essential for the effective initiation of host defence mechanisms against infection. Understanding how cells detect cytosolic DNA to trigger innate immune gene transcription has important implications - not only for comprehending the immune response to path …
Fights any foreign invader and thus is non-specific. Innate immunity and adaptive immunity are the two categories of the immune system of animals. There are both similarity and difference between innate and adaptive immunity. Memory usage: 1408.09KB, Persistent Low Grade Fever: Causes and Remedies, Humoral immunity, consisting of B cells and plasma cells, Cell mediated immunity, consisting of T cells, which further matures into helper T cells, suppressor T cells and cytotoxic T cells. Innate immunity includes all the defence elements with which an individual is born. Innate immunity is also known as genetic immunity or familial immunity. Innate immunity means the non-specific immunity.it is present at the time of birth. Difference Between Adaptive Immunity and Innate Immunity: Innate Immunity. Humans have a high degree of resistance to foot-and-mouth disease, for example, while the cattle and sheep with which they may be in close contact suffer in the thousands from it.Rats are highly resistant ...
Kanazawa, Japan - Although the innate immune system is the front line of defense against microbial infections, the complex mechanisms of innate immunity are incompletely understood. In a new study, researchers from Kanazawa University synthesized and characterized the bacterial toxin Monalysin to enable the study of how the innate immune system and toxin-producing bacteria interact with each other.. The innate immune system detects microbial infections through sensing either microbial molecules (pathogen-associated molecular patterns, or PAMPs) or host signaling molecules that are released from damaged host cells (damage-associated molecular patterns, or DAMPs). The bacterium Pseudomonas entomophila has been utilized as a tool to study the mechanisms of DAMPs in the gut. P. entomophila infects insects and damages intestinal cells using a pore-forming toxin called Monalysin. Monalysin is secreted as an inactive pro-toxin, which is then activated by certain proteins called proteases. Although the ...
The HIV Immune Networks Team (HINT) is a multidisciplinary group comprised of thirteen investigators located in seven different institutions across the United States. Our aim is to understand the early immune response to HIV-1 infection using a systems biology approach. To accomplish this goal, we have assembled a team of world experts in the areas of systems biology, virology, immunology, human genetics, and computational biology. We aim to develop rigorously-validated computational models that reflect, as well as predict, the early innate immune response to HIV-1 exposure. These models will provide valuable new insights into how our innate immune system responds to HIV-1 infection, and ultimately dictate course of infection and disease progression. A mathematical understanding of these dynamic molecular circuits will aid in the development of HIV-1 vaccines and antiviral therapeutics.. ...
Numerous human genetic and acquired diseases could be corrected or ameliorated if viruses are harnessed to safely and effectively deliver therapeutic genes to diseased cells and tissues in vivo. Innate immune and inflammatory response represents one of the key stumbling blocks during the development of viral-based therapies. In this review, current data on the early innate immune responses to viruses and to the most commonly used gene therapy vectors (using adenovirus and adeno-associated virus) will be discussed. Recent findings in the field may help develop new approaches to moderate these innate immune anti-viral responses and thus improve the safety of viral vectors for human gene therapy applications.
Multicellular organisms, in order to survive, have developed a wide range of defense mechanisms that have the ability to rapidly recognize pathogens and mount an early effective antimicrobial response by preventing infection, destroying the invading pathogens or neutralizing their virulence factors. These functions are the domain of innate immune cells such as macrophages, dendritic cells (DCs), neutrophils, natural killer (NK) cells and NKT cells. Although the innate immune system was described by Metchnikoff over a century ago, there are still at least three fascinating problems in host innate defense against microbial invasion. First, how does the host innate defense recognize and destroy many different pathogens? Second, how does the host discriminate between constituents of the external world, microbial non-self, and the constituents of self? And third, how does the innate immune system direct and dictate the type and magnitude of the adaptive immune responses. The main focus of our ...
Toll-like receptors (TLRs) are major receptors of the host innate immune system that recognize conserved pathogen-associated molecular patterns (PAMPs) of invading microbes. Activation of TLR signaling culminates in the expression of multiple genes in a coordinate and kinetically defined manner. In this review, we summarize the current studies describing the chromatin landscape of TLR-responsive inflammatory genes and how changes to this chromatin landscape govern cell type-specific and temporal gene expression. We further elaborate classical endotoxin tolerance and epigenetic mechanisms controlling tolerance and interferon priming effects on inflammatory promoters.
The cellular localisation of many innate signalling events following viral infection has yet to be elucidated, however there has been a few cases in which membranes of certain cellular organelles have acted as platforms to these events. Of these, lipid droplets (LDs) have recently been identified as signalling platforms for innate TLR7 and 9 signalling. Despite their wide range of similar roles in various metabolic pathways, LDs have been overlooked as potential platforms for antiviral innate signalling events. This study established an in vitro model to evaluate the efficiency of the early innate immune response in cells with reduced LD content to the viral mimics, dsDNA and dsRNA, and Sendai viral infection. Using RT-qPCR, the expression of IFN- and IFN-λ was quantified following stimulation along with the expression of specific ISGs. Luciferase based assays evaluated the combined expression of ISRE-promoter driven ISGs under IFN- stimulation. Cellular LD content did not alter the entry of ...
Dr. Marzena Pazgier is an Assistant Professor at the Institute of Human Virology and the Department of Biochemistry and Molecular Biology of the University of Maryland School of Medicine. She obtained her doctoral degree in Technical Chemistry of Sciences at the Technical University of Lodz, Poland, in 2001. In 2002 she joined the Macromolecular Crystallography Laboratory at NCI-Frederick, NIH, as postdoctoral fellow to study structures and function proteins engaged in early innate immune responses, such as defensins. At the Institute of Human Virology Dr. Pazgier continued studies on defensins, but also expanded her research to explore role of Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC) in preventing or modulating HIV-1 infection. Her research program combines structural biology by X-Ray crystallography and contemporary biophysical and protein engineering techniques.. Currently Dr. Pazgier is the Project Leader within the Lewis CAVD Consortium where ...
The purpose of the program project grant is to evaluate the placental, decidual and maternal immune interactions from a new perspective, that a positive interaction between placental and maternal components exist together to support and protect pregnancy and does not represent the classic graft/rejection interaction. Trophoblast cells, decidual (stromal and endothelial) cells, as well as cells of the innate immune system, communicate with each other throughout a network of cytokines and chemokines. Such crosstalk occurs through the expression of innate immune sensors, known as Toll-like Receptors (TLRs) that are expressed at the maternal-fetal interface and serve as sensors for the recognition and response to the environment throughout implantation and gestation. Our studies focus on the expression, regulation and function of TLRs in each of the cellular components of the maternal-fetal interface, and to evaluate their role in pregnancy success providing a complete picture of molecular ...
In this study we focused on the signaling of V antigen-induced innate immunity responses. For the first time we demonstrate that a bacterial nonlipidated protein associated with virulence and derived synthetic oligopeptides are capable to induce IL-10 production via TLR2/CD14 signaling. In contrast to the pseudomonas rPcrV, rLcrV (range of activity: 10-100 nM) transmits signaling via TLR2 in a CD14-dependent manner leading to IL-10 induction which finally causes TNF-α suppression thus probably enabling yersiniae to evade the host innate immune system. Several lines of evidence obtained in vitro both in murine and human cell systems support this conclusion: (a) Only CD14-TLR2-cotransfected HEK 293 cells, but not cells transfected with TLR2 alone responded with NF-κB-dependent ELAM-1 promoter luciferase activity upon rLcrV stimulation. (b) Blocking anti-CD14 monoclonal antibodies, but not nonblocking isotype anti-CD14 antibodies completely abolished TNF-α suppression in LcrV-treated MonoMac-6 ...
Studencka, M.; Konzer, A.; Moneron, G.; Wenzel, D.; Opitz, L.; Salinas-Riester, G.; Bedet, C.; Krüger, M.; Hell, S. W.; Wisniewski, J. R. et al.; Schmidt, H.; Palladino, F.; Schulze, E.; Jedrusik-Bode, M. A.: Novel roles of Caenorhabditis elegans heterochromatin protein HP1 and linker histone in the regulation of innate immune gene expression. Molecular and Cellular Biology 32 (2), pp. 251 - 265 (2012 ...
Studencka, M.; Konzer, A.; Moneron, G.; Wenzel, D.; Opitz, L.; Salinas-Riester, G.; Bedet, C.; Krüger, M.; Hell, S. W.; Wisniewski, J. R. et al.; Schmidt, H.; Palladino, F.; Schulze, E.; Jedrusik-Bode, M. A.: Novel roles of Caenorhabditis elegans heterochromatin protein HP1 and linker histone in the regulation of innate immune gene expression. Molecular and Cellular Biology 32 (2), pp. 251 - 265 (2012 ...
The Toll/interleukin-1 receptor/resistance protein (TIR) domain is a protein-protein interaction domain consisting of 125-200 residues, widely distributed in animals, plants and bacteria but absent from fungi, archea and viruses. In plants and animals, these domains are found in proteins with functions in innate immune pathways, while in bacteria, some TIR domain-containing proteins interfere with the innate immune pathways in the host. TIR domains function as protein scaffolds, mostly involving self-association and homotypic interactions with other TIR domains. In the last 15 years, the three-dimensional structures of TIR domains from several mammalian, plant and bacterial proteins have been reported. These structures, jointly with functional data including the identification of interacting proteins, have started to provide insight into the molecular basis of the assembly of animal and plant immune signaling complexes, and for host immunosuppression by bacterial pathogens. This review focuses ...
Dr. Darveau received his Ph.D. in bacteriology from Washington State University and did his postdoctoral research in the Department of Microbiology at the University of British Columbia studying structure/function relationships in the outer membrane of Pseudomonas aeruginosa. He is a Research Professor in the Department of Periodontics.. Our research is centered on the innate host response to microbial colonization and infection. We are keenly interested in the inflammatory component of the innate host response. Our laboratory studies both the microbial components that elicit inflammation and the activation pathways employed by the host in response to different microbial components. We study responses to both commensal and pathogenic bacteria. We employ biochemical isolation and analytical techniques to characterize the microbial components. Examples of microbial components that we have studied are lipopolysaccharide form gram negative bacteria and lipoteichoic acid from gram positive bacteria. ...
Product Description specificalInvolved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. The ATG12- ATG5 conjugate also negatively regulates the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Also plays a role in translation or delivery of incoming viral RNA to the translation apparatus. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for ...
Chronic kidney disease is widespread in the western world with bacterial infection and sepsis as common complication. It has been shown that innate immune defence, represented by dysfunction of neutrophil granulocytes, is impaired in chronic kidney disease. Another impact of chronic kidney disease on innate immunity is the chronic activation of neutrophils leading to high levels of inflammatory cytokines, thus contributing to protein oxidation. Oxidation of human serum albumin (HSA), the major plasma protein, occurs in chronic kidney disease and leads to further activation of neutrophils. Another important impact of HSA oxidation is the decrease of its binding capacity leading to impaired detoxification ability of albumin. This includes reduced clearance of endotoxin, a major component of the gram negative bacterial cell wall. Circulating endotoxin is recognized by complex formation with lipopolysaccharide binding protein (LBP) followed by binding to CD14 and toll-like receptor (TLR) 4. High ...
1 Functions of the innate and adaptive arms of the immune system. Innate Immune Cells Adaptive Immune Cells Immune recognition Immune effector mechanisms Immune regulation Immunological memory response - particularly the adaptive arm of the immune response - occurs in the secondary lymphoid organs draining the site of infection. The immune system has evolved a number of effector mechanisms capable of destroying pathogenic organisms. 1). The innate arm of the immune system recognises pathogens non-specifically and generates immediate generic mechanisms of pathogen clearance. Many cytokine receptors are dimeric, and the chains making up some of the cytokine receptors are promiscuous. For example, the common ␥ chain (CD132) is shared by a number of cytokine receptors (notably the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21), and the IL-4R chain (IL-4R␣) pairs with IL-␣13R to convey signals in response to IL-13. 8 Adaptive immunity The adaptive immune response differs ...
To differentiate between the contribution of mammary epithelial cells (MEC) and infiltrating immune cells to gene expression profiles of mammary tissue during early stage mastitis, we investigated in goats the in vivo transcriptional response of MEC to an experimental intra mammary infection (IMI) with Staphylococcus aureus, using a non-invasive RNA sampling method from milk fat globules (MFG). Microarrays were used to record gene expression patterns during the first 24 hours post-infection (hpi). This approach was combined with laser capture microdissection of MEC from frozen slides of mammary tissue to analyze some relevant genes at 30 hpi. During the early stages post-inoculation, MEC play an important role in the recruitment and activation of inflammatory cells through the IL-8 signalling pathway and initiate a sharp induction of innate immune genes predominantly associated with the pro-inflammatory response. At 30 hpi, MEC express genes encoding different acute phase proteins, including ...
The consequences of altered ADAR1 function are severe, from embryonic lethality in mice to debilitating neurological disease and systemic interferonopathy in humans with loss-of-function alleles [22, 52], to putative oncogenic roles when overexpressed [31, 53, 54], so it is critical to clearly define the key function(s) of ADAR1. In contrast to the physiologically essential role of transcript recoding by ADAR2, the importance of recoding to the biology of ADAR1 was unknown. In addition to protein recoding, ADAR1 can edit dsRNA substrates resulting in changes in multiple aspects of miRNA biogenesis or function, affect mRNA stability, 3-UTR length and translation, and modify splice site usage in addition to altering dsRNA secondary structures, which have been proposed to interface with the innate immune sensing system [19, 55]. We now demonstrate that the absence of ADAR1-mediated editing is surprisingly well tolerated, once the innate immune sensor MDA5 is deleted. Adar1 E861A/E861A Ifih1 -/- ...
The research group on innate immunity and bacterial infections not only consist of postdocs, PhD students, and technicians. We also offer bachelor and master students the opportunity to follow a trainee internship and to participate in the different research projects. Regardless of the specific subject, being the complement system, phage display, bacterial glycobiology, or phagocyte biology, many techniques and experimental setups are common in the research group. These techniques are both in the field of microbiology and the host defence employing molecular biology (bacterial protein expression, mutagenesis, gene regulation, knock-outs, eukaryotic receptor expression and mutagenesis), protein and carbohydrate chromatography and analysis (including purification of host defence proteins), functional assays using flow cytometry, confocal and electron microscopy, and some in-vivo infection models. The students become a full member of the participating research group with daily supervision. ...
The innate immune mechanism described here clears bacteria and protects against pneumonia. We show that in response to infection, pleural B cells relocate to the lung and produce abundant natural IgM, which is known to protect against infection (Boes et al., 1998; Baumgarth et al., 2000; Fabrizio et al., 2007; Choi and Baumgarth, 2008; Litvack et al., 2011; Schwartz et al., 2012). B cell-derived GM-CSF is the autocrine instructor required for emergency IgM production. Recently identified IRA B cells, which differentiate from B1a B cells in the mouse via direct TLR-dependent pathogen recognition, are key to this process and therefore to early innate immune defense.. GM-CSF was identified in the 1960s as a colony stimulator of granulocytes and mononuclear cells, though not erythrocytes (Bradley and Metcalf, 1966). GM-CSF-deficient mice, which were independently generated by two groups in 1994 (Dranoff et al., 1994; Stanley et al., 1994), show no striking perturbations of hematopoiesis in the ...
Immune sensor proteins are critical to the function of the human innate immune system. The full repertoire of cognate triggers for human immune sensors is not fully understood. Here, Robinson, Zhong, Reversade and team report that the human NLR, NLRP1, is activated by 3C proteases (3Cpros) of enteroviruses. Their findings establish 3Cpros as a pathogen-derived trigger for the human NLRP1 inflammasome and suggest that NLRP1 may contribute to inflammatory diseases of the airway. ...
TY - JOUR. T1 - Effects of tobacco smoking on innate immunity. T2 - A study based on neutrophil phagocytic index. AU - Thakur, Tanu. AU - Bhide, Arpana. AU - Chaudhury, Abhijit. AU - Thota, Asha. AU - Kasala, Latheef. AU - Hulikal, Narendra. PY - 2018/4/1. Y1 - 2018/4/1. N2 - The present study was undertaken to find out the effects of tobacco smoking on innate immune mechanism of the body. A total of 60 adult consenting men in the age group of 30 to 50 years were recruited of which 30 were chronic smokers and the rest were non smoking controls. 5ml of venous blood was drawn from each of the subjects and the following parameters were assessed: phagocytic index of neutrophils (which is an index of neutrophil function and is defined as number of neutrophils positive for ingested microbes per 100 neutrophils), total leucocyte count (TLC), differential count of neutrophils. The values from smokers were compared with those from non-smokers. There was a statistically significant decrease in the ...
Overwhelming inflammatory responses leading to neutrophil invasion are hypothesised to be the main cause of mortality in influenza virus induced acute respiratory distress syndrome (ARDS). Previously, pulmonary surfactant has been shown to modulate inflammatory responses to bacterial agents. The aim of the present study was to investigate the effect of pulmonary surfactant on innate immune responses in an in vitro model of influenza virus infected human airway epithelial cells. Human lung type II alveolar epithelial cells A549 and BEAS-2B human bronchial epithelial cells were infected with influenza A virus H1N1 strains A/Swine/1976/31, A/WSN/33 and A/PR/8/34. Poly I:C, Escherichia coli Ol 11 :B4 LPS and measles virus strain Edmonston were used as cytokine stimulation controls. The effect of pulmonary surfactant was compared to that of dexamethasone. This in vitro study showed that physiological concentrations (up to 500 ug/ml) of clinically approved SP-A and SP-D depleted surfactant ...
Genetic variations in innate immunity genes affect response to Coxiella burnetii and are associated with susceptibility to chronic Q ...
Hepatitis C virus (HCV) infection and alcoholic liver disease synergistically promote the progression of advanced liver disease and non-response to interferon (IFN)-based antiviral therapy. The purpose of this study is to explore how ethanol (EtOH) establishes a favorable environment for HCV replication by deregulating antiviral innate immunity in the hepatocyte. ❧ Results show that not all of the known anti-HCV interferon (IFN) stimulated genes (ISGs), which are the effectors of intracellular innate immunity, are inducible in the hepatocyte. In addition, the mRNA induction of selected anti-HCV hepatocyte-inducible ISGs by IFN is impaired in the presence of EtOH in vitro, though mRNA induction by IFN and impairment by EtOH in vivo can vary from in vitro results. Furthermore, the induction of a potent ISG IRF1 is heterogeneous among hepatocytes in EtOH-fed mice. ❧ In conclusion, EtOH attenuates the ISG response, and this defect in antiviral immunity may be partially attributable to suppressed ...
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum-associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells. The overexpression of TAP1 enhanced virus replication by inhibiting the virus-triggered activation of NF-κB signaling and the production of IFNs, IFN-stimulated genes, and proinflammatory cytokines. TAP1 depletion had the opposite effect. In response to virus infection, TAP1 interacted with the TGF-β-activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the IκB kinase ...
Innate immune genes tend to be highly conserved in metazoans, even in early divergent lineages such as Cnidaria (jellyfish, corals, hydroids and sea anemones) and Porifera (sponges). However, constant and diverse selection pressures on the immune system have driven the expansion and diversification of different immune gene families in a lineage-specific manner. To investigate how the innate immune system has evolved in a subset of sea anemone species (Order: Actiniaria), we performed a comprehensive and comparative study using 10 newly sequenced transcriptomes, as well as three publically available transcriptomes, to identify the origins, expansions and contractions of candidate and novel immune gene families. We characterised five conserved genes and gene families, as well as multiple novel innate immune genes, including the newly recognised putative pattern recognition receptor CniFL. Single copies of TLR, MyD88 and NF-κB were found in most species, and several copies of IL-1R-like, NLR and CniFL
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Innate immunity is characterized by production of type I interferon which is necessary for the stimulation of effective anti-viral host defense. Upon recognition of cytosol viral dsRNA species, RIG-I-Like Receptors (RLRs), as well as many co-regulators, are recruited to adaptor protein IPS-1 and trigger innate immune responses. FADD (Fas associated with death domain) and RIP1 (receptor-interacting protein 1), have been reported to be recruited to this IPS-1 complex during viral infection and essential for optimal RLR signaling. Here we reported a novel type I interferon inducible DExD/H family helicase DDX24, which was found and confirmed to specifically associate with FADD through yeast two hybrid system and co-immunoprecipitation. Overexpression of DDX24 negatively regulates dsRNA induced type I IFNs signaling, while knockdown of DDX24 by siRNA has the opposite effect. Moreover, Plaque assays of virus titer consistently demonstrate that DDX24 also negatively regulates the cellular antiviral response.
TY - JOUR. T1 - Lgt processing is an essential step in Streptococcus suis lipoprotein mediated innate immune activation. AU - Wichgers, P.J.. AU - Rebel, J.M.J.. AU - Smits, M.A.. AU - van Putten, J.P.. AU - Smith, H.E.. PY - 2011. Y1 - 2011. N2 - Background Streptococcus suis causes invasive infections in pigs and occasionally in humans. The host innate immune system plays a major role in counteracting S. suis infections. The main components of S. suis able to activate the innate immune system likely include cell wall constituents that may be released during growth or after cell wall integrity loss, however characterization of these components is still limited. Methology/Principal Findings A concentrated very potent innate immunity activating supernatant of penicillin-treated S. suis was SDS-PAGE fractionated and tested for porcine peripheral blood mononucleated cell (PBMC) stimulating activity using cytokine gene transcript analysis. More than half of the 24 tested fractions increased IL-1ß ...
The á2â1 integrin is expressed on many cell types throughout the immune system. Expression of the á2â1 integrin on mast cells is required for the early innate immune response to Listeria monocytogenes. Interaction between the á2â1 integrin and Listeria occurs through C1q within a Listeria immune complex, but is not sufficient for activation suggesting an additional co-receptor is required for activation. We demonstrate that Listeria immune complex activation of mast cells occurs through crosstalk between the á2â1 integrin and c-met. The best described mechanism of mast cell activation is IgE-mediated degranulation. We examined the mechanism of mediator release by mast cells following activation by Listeria immune complex. Activation by Listeria immune complex results in á2â1 integrin-dependent release of IL-6 from a granule pool that is distinct from known mast cell granules, identifying a novel population of mast cell granules. The á2â1 integrin-dependent early innate immune ...
Toda la información sobre las últimas publicaciones científicas de la Clínica Universidad de Navarra. Surfactant protein d, a marker of lung innate immunity, is positively associated with insulin sensitivity
Looking for online definition of innate immunity in the Medical Dictionary? innate immunity explanation free. What is innate immunity? Meaning of innate immunity medical term. What does innate immunity mean?
Innate immunity is the first-line, non-specific response to any breach of our bodies. Conclusion Cells of both the innate and adaptive immune systems are false. Besides their contribution to host defence via innate mechanisms, MC also promote adaptive immune responses through physical interactions with CD4 and CD8 T cells (Fig. Innate and adaptive immunity is a very complex biological process. 5. The ratio of T cells to B cells is. Humoral adaptive immunity vs. cell-mediated adaptive immunity. ... they are on the cell surface and help the immune system determine self not self Adaptive immunity refers to antigen-specific immune response. Humoral adaptive immunity vs. cell-mediated adaptive immunity. If youre seeing this message, it means were having trouble loading external resources on our website. 3: Innate immunity is orchestrated through phagocytes (Macrophages, and Neutrophils) and Natural Killer cells. Cell mediated immunity, consisting of T cells, which further matures into helper T ...
Upon viral infection, the major defense mounted by the host innate immune system is activation of the IFN- and apoptosis-mediated antiviral pathway. In order to complete their life cycle, viruses that are obligatory intracellular parasites must modulate these host immune responses. We have previously shown that the γHV68 latency-associated M2 protein effectively downregulates STAT1 and STAT2, resulting in the inhibition of type I and II IFN-mediated transcriptional activation. Here, we demonstrate that M2 interacts with ATM, a DNA damage signal transducer, and the DDB1/COP9/cullin DNA damage effector complex. This interaction blocked DNA damage-sensing activity as well as DNA damage repair activity, thereby rendering cells resistant to DNA damage-induced apoptosis. These results indicate that γHV68 encodes M2, a latency-associated gene, to antagonize both IFN- and apoptosis-mediated host innate immunities and thus is important in establishing and maintaining viral latency in infected ...
Acute lower respiratory tract infections cause a terrible public health burden at present, with potential for worse in the coming years. The outcome of these infections is determined by innate immune responses (such as neutrophil recruitment and activation), necessary for host defense but also contributing to lung injury. Innate immune responses in the lungs require the coordinated expression of diverse mediators including adhesion molecules, chemokines, colony stimulating factors, and cytokines that are absent or present only at low levels in uninfected lungs, but are expressed at high levels during infection. Similar mediators are induced during most lung infections, although individual mediators can have different roles during different infections. The coordinated expression suggests programs of gene regulation. NF-kappaB transcription factors are critical to the gene expression program directing innate immunity in the lungs, with RelA inducing innate immunity genes mediating host defense and ...
BACKGROUND: Nucleotide binding oligomerisation domain 2 (NOD2; also known as CARD15) mutations are associated with Crohns disease but how mutations cause disease is poorly understood. Innate immune responses are reportedly enhanced by combined NOD2 ligand (muramyl dipeptide, MDP) and Toll-like receptor 4 ligand (TLR4, lipopolysaccharide) stimulation. Intestinal TLR signalling has a dual role-maintaining intestinal homeostasis and protection from injury as well as initiating inflammatory responses. TLR9 is functional in the intestinal epithelium where it is most strongly expressed in Paneth cells. AIMS: To study possible interactions between CpG DNA (TLR9 ligand) and MDP using primary human cells of differing NOD2 genotypes. SUBJECTS: NOD2 wild-type healthy controls (n = 7) and NOD2 homozygous Crohns disease patients (n = 19), age and sex matched. METHODS: Peripheral blood mononuclear cells were stimulated with CpG DNA and MDP. Cytokines were measured by enzyme linked immunosorbent assay. RESULTS:
Viral recognition by the host innate immune system has become an exciting and growing area of research focus in recent years. It is now apparent that multiple pattern recognition receptor (PRR) families, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), contribute significantly to viral detection by sensing viral proteins and nucleic acids, leading to induction of cytokines and type I interferons (IFNs). Of particular current interest is the sensing of viral DNA within infected cells, since the PRRs responsible for this are only partially defined. Recently RNA polymerase III (Pol III) was shown to transcribe some viral DNAs into RNA for detection by RIG-I, leading to IFN induction. Another novel mechanism of viral DNA recognition unveiled, leading to proinflammatory cytokine production, involves the PYHIN family member AIM2 ...
Systemic autoimmunity is thought to result from a mix of genetics, environmental factors and stochastic events [6]. Given the multitude of susceptibility genes, symptoms and immunological abnormalities, it is clear that numerous pathogenic pathways contribute to systemic autoimmune disease [5, 11, 12]. A major thrust of systemic autoimmunity research has centered on elucidation of abnormalities in the adaptive immune response [13, 14]. However more recent research has identified the innate immune response as a major player in the initiation and expansion of systemic autoimmune pathology [4, 5, 9, 15, 16].. The current paradigm for the disease process of idiopathic systemic lupus-like autoimmunity argues for a central role of type I IFN [15, 17, 18]. This is based on the early observation of increased expression of IFN-α inducible genes (or IFN signature) in the peripheral blood cells of patients with SLE [17]. The type I IFN signature is found in 60% to 70% of patients with SLE, ...
Matrix Metalloproteinase (MMP)-12 activity has been attributed to cleavage of cytokines, and digestion of extracellular matrix components related to the pathogenesis of diverse conditions, including atherosclerosis and aortic aneurysms. We hypothesise that a major role for MMP-12 is its regulation of gene expression during the innate antiviral immune response, controlling the secretion of alpha interferon (IFN-α) during enterovirus induced myocarditis. We employed an MMP-12 knockout mouse model of enteroviral myocarditis to determine the role of MMP-12 during the antiviral response. Electromobility shift assay (EMSA), Chromatin immunoprecipitation PCR (ChIP) and ChIP combined with Illumina-Solexa sequencing (ChIP-seq) were used to analyse the regions of the human genome bound by MMP-12 under control and virus infected conditions. Traditional immunofluorescence microscopy and molecular biology approaches were also used to confirm the results of the genomic ChIP studies. Coxsackievirus type-B3 ...
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Full Text PA-97-079 INNATE IMMUNITY NIH GUIDE, Volume 26, Number 24, July 25, 1997 PA NUMBER: PA-97-079 P.T. 34 Keywords: Immunology National Institute of Allergy and Infectious Diseases National Institute of Dental Research PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Dental Research (NIDR), National Institutes of Health (NIH), invite applications for research studies of the innate immune system. Two general systems of immune recognition have been selected through evolution: innate immunity and acquired immunity. The innate immune system provides broad, but relatively nonspecific host defenses that lack the properties of antigenic specificity and immunologic memory that characterize acquired immunity. However, recent discoveries point to many robust mechanisms of innate immunity and have highlighted important functional links between the innate and acquired immune responses. The purpose of the PA is to support basic and preclinical ...
Abstract: Infection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1-24). We identified the low frequency haplotype AACCAT significantly associated with recurrent ...
The NF-kappaB pathway has been shown to play a critical role in both adaptive and innate immunity and has been implicated as a focal point for induction of lung inflammation by a variety of inflammatory stimuli; however, the role of NF-kappaB in specific lung cell types remains unclear. We hypothesized that individual cell types in the lungs make important and unique contributions to the NF-kappaB dependent innate immune response. To determine the temporal and cell specific activation of NF-kappaB in vivo, an NF-kappaB reporter mouse in which expression of an enhanced green fluorescent protein (eGFP)/luciferase fusion protein cDNA driven by an NF-kappaB inducible promoter (NGL mouse) was generated. NF-kappaB activity was detected in intact, anesthetized animals by bioluminescence imaging and at the cellular level by detection of GFP on lung tissue sections. Using Eschericia coli lipopolysaccharide (LPS) and Pseudomonas aeruginosa models of lung inflammation, the timing and duration of NF-kappaB ...
Learn about increasing the immunity system of the body with different techniques for various conditions. Immunity can also be improved naturally or by consuming immunity boosting foods
BACKGROUND/AIMS: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-β) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. METHODS: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells ...
Advancing knowledge regarding the biology of Crohns Disease (CD) has identified that the hosts innate immunity may impact on the development of intestinal inflammation. Pattern recognition receptors and the Toll-like receptors are able to detect both gram positive and gram negative bacteria, yeasts and flagellin and respond by activation of the innate immune system. By identification of the unmethylated CpG dinucleotide sequences found in bacteria, lymphocytes are stimulated, proinflammatory cytokines like interleukin (IL)-12 and the interferons are induced, and both the mucosal and host defences against the invading pathogens are increased.. A body of evidence from clinical and experimental observations indicates a role for endogenous digestive microflora in the pathogenesis of inflammatory bowel disease (IBD). The distal ileum and the colon are the areas with highest luminal bacterial concentrations and represent the sites of inflammation in IBD. Probiotics have been shown to reduce ...
Professor Paul Hertzog is a NHMRC Senior Principal Research Fellow, Head of the Centre for Innate Immunity and Infectious Diseases, Associate Director of the Hudson Institute of Medical Research, Professor at Monash University and an Adjunct Professor of the Chinese Academy of Sciences. He obtained his PhD from the University of Melbourne and undertook postdoctoral positions in the USA at the Eppley Institute of Cancer Research and at the University of York in the UK. He has an established record of research on innate immune responses in infection, inflammation and cancer, particularly regulation by interferons. His groups work has been published in eminent journals including Cell, Science, Nature Immunology, Nature Medicine, Immunity, and the Journal of Clinical Investigation, etc. This work resulted in Professor Hertzog being awarded the international 2013 Milstein Award for Excellence in Interferon and Cytokine Research. Professor Hertzog is co-founder of the Victorian Infection and Immunity ...
Pathogen recognition receptor signaling induces p38 kinase-dependent priming phosphorylation of IFNAR1.(A) KR-2 cells were treated with CpG (10 µM for 30 min)
CIIID is a scientific research center based at the University of Washington School of Medicine in Seattle, where researchers from diverse scientific backgrounds work together and focus their expertise to discover how innate immunity dictates the bodys response to infectious disease or impacts autoimmune disease. CIIID scientists have access to four world class service cores with specific expertise in innate immunity: Human Cell Signaling, Transgenic Mouse Core, Immuno-informatics & Computational Modeling Core, and Translation Core. The CIIID also features an Education Core that hosts multiple programs for middle and high school students to conduct research in innate immunity. For additional information about The Center for Innate Immunity and Immune Disease, visit CIIID website at https://ciiid.washington.edu/. ...
By virtue of its direct contact with the environment, the lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated by the innate and adaptive arms of the immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels of microbial and non-infectious antigens throughout the respiratory tract and mediate host innate immunity. Selective induction of inflammatory responses to harmful environmental exposures and tolerance to innocuous antigens are required to maintain tissue homeostasis and integrity. Conversely, dysregulated innate immune responses manifest as sustained and self-perpetuating tissue damage rather than controlled tissue repair. In this article we review aspects of Toll-like receptor function that are relevant to the development of acute lung injury and chronic obstructive lung diseases as well as resistance to frequently associated microbial infections.
Three different families of pattern recognition receptors, toll-like (TLRs), Nod-like (NLRs), and RIG-I-like, initiate innate immunity, the inborn host response to common pathogens such as viruses, bacteria, and fungi. These receptors recognize and bind pathogen-associated molecular patterns (PAMPs) such as viral DNA and RNA, or bacterial and fungal cell wall components. PAMP-receptor binding activates the innate immune response, initiates downstream signaling, and induces expression of inflammatory cytokines as well as the type-I interferon response. The innate immune system attracts immune cells to the site of infection, and activates the adaptive immune response. This initial immune response is essential to combat a novel foreign pathogen. Dysregulation of innate immune processes can lead to widespread infection, sepsis, and immunodeficiencies ...
Three different families of pattern recognition receptors, toll-like (TLRs), Nod-like (NLRs), and RIG-I-like, initiate innate immunity, the inborn host response to common pathogens such as viruses, bacteria, and fungi. These receptors recognize and bind pathogen-associated molecular patterns (PAMPs) such as viral DNA and RNA, or bacterial and fungal cell wall components. PAMP-receptor binding activates the innate immune response, initiates downstream signaling, and induces expression of inflammatory cytokines as well as the type-I interferon response. The innate immune system attracts immune cells to the site of infection, and activates the adaptive immune response. This initial immune response is essential to combat a novel foreign pathogen. Dysregulation of innate immune processes can lead to widespread infection, sepsis, and immunodeficiencies ...
Toll-like receptors are pattern recognition receptors that play a vital role in innate immunity pathways as they detect pathogen-associated molecular patterns on bacteria, fungi, protozoa, and viruses. Many TLRs are expressed on the plasma membrane while TLR7, TLR8, and TLR9 are expressed within the cell on the endosome. Upon activation, TLRs dimerize and bind to TIR-containing adaptor proteins including TRIF, TIRAP, TRAM, and MyD88. Downstream signaling through IKKs and the NFκB pathway results in the production of inflammatory cytokines and interferons.. Click on the poster below to view the interactive version.. ...
QUIET PRIMING BY NEXT GENERATION VACCINE ADJUVANTS. Dr. Mitchell is dedicated to discovering how the immune system can be safely stimulated to fight disease. His work is most relevant to development of vaccine adjuvants, which are used in modern vaccines to boost their effectiveness without causing harm or unnecessary discomfort.. Modern immunology is guided by the paradigm that innate immunity against microbes is necessary for adaptive immunity to be generated in individuals for long term protection against re-infection. Dr. Mitchells research to advance safe immunostimulation is based on the idea that partial signaling through receptors of the innate immune system can achieve sufficient priming of the adaptive immune response so as to be protective while minimizing counterproductive effector responses by innate immune cells such as neutrophils and macrophages. TLR4-MD2, the innate receptor for bacterial LPS, is currently a focus of research for the Mitchell lab because it is targeted by a ...
Terada T, Nii T, Isobe N, Yoshimura Y (2018) Changes in the expression of avian β-defensin (AvBDs) and proinflammatory cytokines and localization of AvBD2 in the intestine of broiler embryos and chicks during their growth. Journal of Poultry Science (in press). Kang Y , Nii T, Isobe N, Yoshimura Y (2018) Effects of TLR ligands on the expression of cytokines and possible role of NFκB in its process in the theca of chicken follicles. Journal of Poultry Science (in press). Matsukawa S, Ueno K, Sugino T, Yoshimura Y, Isobe N (2018) Effects of colostrum whey on immune function in the digestive tract of goats. Animal Science Journal (in press). Elgawish RA, Ogata Y, Hidaka T, Nii T, Yoshimura Y, Isobe N (2018) Changes in plasma concentrations of S100A7 and S100A8 in dairy cows during pregnancy. Reproduction in Domestic Animals (in press). Elhamouly M, Terada T, Nii T, Isobe N, Yoshimura Y (2018) Innate antiviral immune response against infectious bronchitis virus and involvement of prostaglandin E2 ...
Recognition and degradation of viral RNA are essential for antiviral innate immune responses. Zinc-finger proteins (ZFPs) are gaining intensive concern because they are a..
Nitric oxide (NO) is a major mediator of host innate immunity with antimicrobial activity against a broad range of pathogens. Specific targeting of protein metal centers, thiols, and other radicals can disrupt microbial metabolism and limit pathogen growth during infection. The opportunistic pathogen Staphylococcus aureus is relatively resistant to NO-mediated growth inhibition, yet NO remains important to control infection. A possible mechanism by which host NO is protective, beyond growth inhibition, may be through the direct targeting of systems that regulate the production of virulence factors, such as toxins. In Staphylococcus aureus, cell-to-cell communication known as quorum sensing regulates virulence and determines whether interactions with a mammalian host are commensal or pathogenic. Despite the importance of quorum sensing to infection, little is known about how host immunity affects inter-bacterial communication. In this thesis, I show that NO, a bacteriostatic effector of innate ...
Lgt processing is an essential step in Streptococcus suis lipoprotein mediated innate immune activation. PLoS One. 2011;6(7):e22299 ...
Previous observations in this laboratory showed that injection of culture-derived trypomastigotes (CT), in CBA/J mice, induced an early increased resistance that was detected 24-72 hr after antigen injection and permitted mice to survive a challenge of 105 blood trypomastigotes (BT) corresponding to 2000 LD50%. Present experiments were conducted to determine the optimal conditions for inducing this early resistance and to investigate the early morphological changes which occurred in blood and lymphoid organs of mice infected with either BT or CT. Among nine antigens tested, only living CT showed a protective effect permiting most of mice to survive 30 days after BT challenge, while control mice injected with PBS or other antigens died at 10 ± 1 days. A dose-response relationship was seen when different doses of CT were tested, higher doses of CT inducing higher survival and lower parasitemia. Injection of CT by either an im or ip route induced similar degrees of resistance but significantly ...
Adaptive- B and T cells - slow to respond- … Innate and adaptive immunity is a very complex biological process. Although, as a group, pattern-recognition receptors (PRRs) can recognize many pathogens, the innate … Antigen receptors are genetically rearranged clonal receptors that bind to antigen displayed in. Innate immunity is always present in the body while adaptive immunity only occurs in response to exposure to an external factor. The potency of adaptive immunity is very high. Test your knowledge and determine where to start. Over the last week, she had been feeling tired and found it difficult to stay awake in class. First, lets start with innate immunity… The adaptive immune response is meant to attack non-self pathogens but can sometimes make errors and attack itself. This way the defense respon… Innate vs. adaptive immunity. If youre seeing this message, it means were having trouble loading external resources on our website. Types of Immunity and the Immune System. The early ...
Dr. Viswanathans research efforts over the past 12 years have focused on the mechanisms of pathogenesis of the diarrheal disease pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC). His laboratory characterized EPEC and EHEC virulence factors (specifically those secreted into host cells) and evaluates their effect on host cell physiology including barrier function, cell death pathways, and effects on innate immune responses. His specialization is innate immune signaling by intestinal epithelial cells in vitro and in vivo, and includes the use of cutting-edge technologies such as in vivo phosphoproteomics, and single-cell manipulation during bacterial infection. He also offers a very popular upper-division course in pathogenic bacteriology, and actively mentors undergraduate and graduate students, and post-doctoral fellows at the UA. Keywords: Pathogenic E. coli, Clostridium difficile, infection, host-pathogen interactions ...
Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK ...
Innate immunity employs Toll-like receptors (TLRs) and Nod-like receptors (NLRs), both families of so-called pattern recognition receptors (PRRs), to detect a variety of different exogenous and endogenous insults. Exogenous insults include bacteria, viruses and fungi.. Upon engagement of their cognate microbe-derived molecular ligands, PRRs initiate distinct intracellular signalling pathways via receptor-proximal adaptor molecules, and subsequent NF-kB- and IRF-mediated gene transcription activates immediate innate immune responses and primes adaptive immunity. Since the discovery of human TLRs in 1997, other families of mainly cytosolic pattern recognition receptors (PRRs) have been described, for example, the RIG-I-like receptors (RLRs), Nod/NACHT-LRR-like receptors (NLRs) and AIM2-like receptors (ALRs). Together with TLRs, these PRR fulfill the important function of immune surveillance in the innate immune system and mark the first line of immune detection for most microbes. Apart from their ...
Adaptive immunity towards tuberculosis (TB) has been extensively studied for many years. In addition, in recent years the profound contribution of innate immunity to host defence against this disease has become evident. The discovery of pattern recognition receptors, which allow innate immunity to tailor its response to different infectious agents, has challenged the view that this arm of immunity is nonspecific. Evidence is now accumulating that innate immunity can remember a previous exposure to a microorganism and respond differently during a second exposure. Although the specificity and memory of innate immunity cannot compete with the highly sophisticated adaptive immune response, its contribution to host defence against infection and to vaccine-induced immunity should not be underestimated and needs to be explored. Here, we present the concept of trained immunity and discuss how this may contribute to new avenues for control of TB.. ...
Adipose tissue of an organism plays a major role in regulating physiologic and pathologic processes such as metabolism and immunity by producing and secreting a variety of bioactive molecules termed adipokines. One highly conserved family of adipokines is adiponectin/ACRP30 and its structural and functional paralogs, the C1q/tumor necrosis factor-alpha-related proteins (CTRPs) 1-7. Unlike adiponectin, which is expressed exclusively by differentiated adipocytes, the CTRPs are expressed in a wide variety of tissues. These proteins are thought to act mainly on liver and muscle tissue to control glucose and lipid metabolism. An analysis of the crystal structure of adiponectin revealed a structural and evolutionary link between TNF and C1q-containing proteins, suggesting that these proteins arose from a common ancestral innate immunity gene. CTRP5 has been suggested to be involved in age-related macular degeneration.
Natural killer (NK) cells are innate immune system lymphocytes with an integral role in host defense against HIV infection. and promote the cytotoxic features that Rabbit polyclonal to JAK1.Janus kinase 1 (JAK1), is a member of a new class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain.The second phosphotransferase domain bears all the hallmarks of a protein kinase, although its structure differs significantly from that of the PTK and threonine/serine kinase family members. kill focus CBR 5884 on cells. Once older, NK cells circulate in the tissue and bloodstream even though surveying for contaminated or malignant cells. Although NK cells are formidable players in the immune system response against infections, genetically modifying NK cells expressing CARs could improve NK cell targeting of malignant and infected cells. Within this review, the function is certainly talked about by us of NK ...