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). ...
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 ...
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...
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.. ...
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 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 ...
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 ...
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. ...
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 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 ...
... responses to tumors and virus-like infections. been determined, including NKp30CN7-L6, great cell lectin-like receptor G1Ccadherin, and NKp80CAICL. Right here, we explain crystal clear constructions established to day of NK cell receptors destined to MHC, MHC-related, and non-MHC ligands. Jointly, these constructions reveal the varied solutions that NK receptors possess created to understand these substances, therefore allowing the legislation of NK cytolytic activity by both sponsor and virus-like ligands. discussion), but also types on the same cell (discussion) (59, 60), as discussed below. LILR Reputation of UL18, a Viral MHC-I Mirror Among the bacteria that possess attained LY 2874455 great achievement in inventing strategies for resistant evasion are the cytomegaloviruses, whose genomes ITGAM encode necessary protein that get in the way with both NK T-cell and cell identification, as well as antigen application and ...
The investigators hypothesize that neutrophils and monocytes developed under the influence of Interferon- gamma-1b (IFN-γ-1b, Actimmune*) in vivo will display
Ruth R. Montgomery is a cellular immunologist with particular expertise in use of novel technology for human translational studies. Her research employs systems wide studies to identify individual differences in immune responses that lead to divergent outcomes to infection. Her group focuses on effects of aging on innate immunity and individual variation influencing susceptibility to West Nile, dengue, and Zika viruses, among others. She has overseen studies of immune responsiveness in human cohorts with successful enrollment of ,1800 healthy individuals. Dr. Montgomerys work is notable for her use of primary human cells to demonstrate immune related mechanisms and illuminate potential avenues for therapeutic interventions. She is Director of the CyTOF facility and Associate Dean for Scientific Affairs ...
Research funded by the U.S. Poultry & Egg Association studied the functional genomic and DNA microarray approach to identify key innate immunity genes as a novel selection method to identify chickens with increased resistance to disease.
Innate immunity is essential for survival in a world filled with microbial pathogens. Cells of the innate immune system are the bodys first responders, arriving soon after foreign elements are detected. Some innate cells find and engulf microorganisms, while others release chemicals that kill the organism directly. Still other cells begin recruiting other specialized immune components to the region. Severe defects in the innate immune system make humans highly susceptible to normally benign infections, which can then become life threatening. For instance, babies born without functional neutrophils one of the primary cell types of the innate immune system do not live more than a few days due to the effects of infection. While the adaptive immune system, which forms the other half of the human immune system, has been studied since the dawn of immunology, it is only in the last few years that researchers have begun to understand the innate immune system in detail, Ulevitch says. The innate immune ...
Innate immunity is the first line of defense against invading pathogens. This defense system can be found in plants, vertebrates, and even invertebrates, but its mechanisms of action are non-specific (unlike an adaptive immune response). This type of response does not help the immune system develop a memory response to help with future recognition of pathogens. Some of the major components of innate immunity include: the complement cascade, phagocytosis, Toll-like receptors, and chemotaxis/extravasation. Skin and stomach acid serve as physical barriers to pathogens. Phagocytosis can lead to antigen presentation, which bridges innate and adaptive immunity. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
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Authors: Bardoel BW, Strijp JA.. During infection, our innate immune system is the first line of defense and has evolved to clear invading bacteria immediately. To do so, recognition is the key element. However, how does the innate immune system distinguish self from nonself, and how does it recognize all bacteria (estimated to be far over a million species)? The answer lies in the recognition of evolutionary conserved structures. In this review, we approach this phenomenon from the bacterial perspective. What are the evolutionary conserved structures in bacteria, and what strategies are there in the human innate immune system to sense these structures? We illustrate most examples both at the functional as well as at the molecular level. Furthermore, we highlight how pathogenic bacteria can evade this recognition to survive better in the human host which in turn can result in life-threatening diseases.. ...
Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions Long Wang,* Chunling Wang,* Jiao Jiao, Yuqing Su, Xiaobo Cheng, Zhenjun Huang, Xinrong Liu, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China*These authors contributed equally to this workAbstract: There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE). The effects of these injections of PE on pharmacokinetics and biodistribution were studied in normal and macrophage-depleted rats. Additionally, we evaluated the antigenic specificity of immunologic tolerance
The spleen is an important site for generating protective immune responses against pathogens. After infection, immune cells undergo rapid reorganization to initiate and maintain localized inflammatory responses; however, the mechanisms governing this spatial and temporal cellular reorganization remain unclear. We show that the strategic position of splenic marginal zone CD169+ macrophages is vital for rapid initiation of antibacterial responses. In addition to controlling initial bacterial growth, CD169+ macrophages orchestrate a second phase of innate protection by mediating the transport of bacteria to splenic T cell zones. This compartmentalization of bacteria within the spleen was essential for driving the reorganization of innate immune cells into hierarchical clusters and for local interferon-γ production near sites of bacterial replication foci. Our results show that both phases of the antimicrobial innate immune response were dependent on CD169+ macrophages, and, in their absence, the ...
The purpose of the innate immunity system is to keep away all pathogens. After, the pathogen makes an appearance in the body, the innate system of defense acts very rapidly. The major point in dealing with the innate system of defense is that it is nonspecific. Therefore, it will approach any pathogen it comes into contact with. The innate systems of defense are very helpful yet we overlook them quite often. The skin is probably the best innate line of defense. It excludes most pathogens from entering the body. Cilia in mucous membranes help sweep out airborne pathogens and dust. Tears, nasal secretions, and saliva are also good because they contain bacteria destroying enzymes. The innate system is also known for phagocytic cells ("phago"-eating, "cyte"-cell) which migrate to affected areas and engulfs the pathogens. Phagocytic cells include: Neutrophils, Macrophages, and Dendritic cells that are part of the white blood cell fraction. Pathogens and infected cells produce chemokines, peptides ...
Autoimmune diseases such as rheumatoid arthritis (RA) are associated with debilitating chronic inflammation, autoantibody production, articular bone erosions and systemic bone loss. The underlying mechanisms and cell types that initiate these diseases are not fully understood, and current therapies mainly address downstream mechanisms and do not fully halt disease progression in all patients. Moreover, previous studies have largely focused on the role of adaptive immunity in driving these diseases, and less attention has been given to the contribution of innate immune pathways such as DNA sensor signaling pathways in initiating and/or perpetuating autoimmunity and erosive inflammatory arthritis. Detection of microbial nucleic acids by DNA sensors such as endosomal toll-like receptors (TLRs) and cytosolic sensors is an early form of antiviral defense. Upon detection of nucleic acid, TLRs dependent on Unc93B and cytosolic sensors dependent on the adaptor stimulator of interferon genes (STING) orchestrate
A research team from the University of California, San Diego School of Medicine has identified a protein produced by cancerous lung epithelial cells that enhances metastasis by stimulating the activity of inflammatory cells. Their findings, to be published in the January 1 issue of the journal Nature, explain how advanced cancer cells usurp components of the host innate immune system to generate an inflammatory microenvironment hospitable for the metastatic spread of lung cancer.
In contrast to nonspecific resistance, immunity (i-mu- ni-te), or specific resistance, is directed at specific antigens. An immune response involves the production of specific cells and substances to attack a specific antigen. Immunity has "memory," that is, if the same pathogen should reenter the body at a ...
Dr. Feng Shaos laboratory is interested in studying molecular mechanisms of bacterial infection and host innate immunity defense. Bacterial pathogens use specialized secretion systems such as type III/IV secretion system to inject effector proteins into host cells, serving as a key and universal virulence mechanism. The effectors usually harbor a unique and potent activity that modulates the function of key signaling molecules in the host, and this plays a critical role in bacterial survival and systemic infections. Using pathogens such as Shigella, Salmonella, Enteropathogenic E. coli (EPEC), Legionella and Burkholderia as the model, we are working to discover and reveal some novel and common biochemical mechanisms utilized by bacterial effectors in modulating host signal transduction pathways. Our recent work has led to several interesting discoveries. 1) The OspF family of type III effectors, conserved in Shigella, Salmonella and the plant pathogen P. syringae, harbors a novel ...
The Journal of Innate Immunity is a bimonthly journal covering all aspects of innate immunity, including: Evolution of the Immune System Pattern Recognition and Signals of Danger Humoral Resp
Through an interplay of signaling molecules and specialized cell types, innate immunity is able to recognize and attempt to remove disease-causing pathogens. In order to fully harness the potential applications of this unique system in animal health, it is important to identify the individual components of innate immunity, and how they combine to mount a successful response.. ...
Immediate and sustained metabolic alterations modulate host defensive responses during infection and malnutrition through metabolic regulations governing by nutrient-sensing machineries. These regulatory mechanisms in both adaptive and innate immune cells are known as immunometabolic regulations. In the past two decades, the explosive progresses in this field uncover the underlying molecular mechanisms and metabolic regulators and, further, reveal how these regulations fine-tune host immunity during vaccination, infection, and disease initiation and progression. In addition, metabolites generated by gut microbiota and metabolic tissues instruct immune responses in periphery and systemic metabolic alterations accompanied with aging could also contribute to insensitivity of immune system. Thus, the interplay between immune cells and metabolic homeostasis in circulation and periphery lead to effective and detrimental immune responses. Moreover, new studies suggest harnessing immunometabolic regulations is
Well, you should remember that macrophage is not typical innate immunity cell. It also acts as APC for activating adaptive immunity. The time when innate immunity is about to stop and adaptive immunity is about to begin is called induced immunity, which dendritic cells and macrophage switch their function from antigen-eating to become antigen-presenting. In adaptive immunity, macrophage does not engulf antigen by phagolysosome mechanism (eating function) anymore like it use to do in innate immunity, it engulf antigen to be processed as peptide and will bring it back to its surface to be presented with MHC (APC function ...