Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae. (1/739)

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.  (+info)

Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis. (2/739)

In shigellosis, the network of cellular interactions mediated by a balance of pro- and anti-inflammatory cytokines or chemokines is clearly tipped toward acute destructive inflammation of intestinal tissues by the bacterial invader. This work has addressed the role played by interleukin-8 (IL-8) in a rabbit model of intestinal invasion by Shigella flexneri. IL-8, which is largely produced by the epithelial cells themselves, appears to be a major mediator of the recruitment of polymorphonuclear leukocytes (PMNs) to the subepithelial area and transmigration of these cells through the epithelial lining. Neutralization of IL-8 function by monoclonal antibody WS-4 caused a decrease in the amount of PMNs streaming through the lamina propria and the epithelium, thus significantly attenuating the severity of epithelial lesions in areas of bacterial invasion. These findings are in agreement with our previous work (31). In contrast to the PMNs, the bacteria displayed increased transepithelial translocation, as well as overgrowth in the lamina propria and increased passage into the mesenteric blood. By mediating eradication of bacteria at their epithelial entry site, although at the cost of severe epithelial destruction, IL-8 therefore appears to be a key chemokine in the control of bacterial translocation.  (+info)

Adaptive immune response to Shigella flexneri 2a cydC in immunocompetent mice and mice lacking immunoglobulin A. (3/739)

Shigella flexneri cydC, which is deficient in cytochrome bd, was rapidly cleared from the lungs of intranasally inoculated mice and was Sereny negative, yet it induced 93% protection against challenge with wild-type S. flexneri. Mice that lack immunoglobulin A (IgA) were fully protected, suggesting that IgA may not be required for adaptive immunity in this model system.  (+info)

Rupture of the intestinal epithelial barrier and mucosal invasion by Shigella flexneri. (4/739)

Invasion of the intestinal barrier by Shigella flexneri involves complex interactions with epithelial and phagocytic cells. Major perturbation of the signals that maintain epithelial integrity permits mucosal invasion, leading to tissue destruction. Expression of this invasive phenotype depends on the secretion of Ipa proteins (invasins), which can trigger entry of the pathogen into epithelial cells by causing massive rearrangement of the host cell cytoskeleton and cause macrophage apoptotic death by direct interaction of IpaB with interleukin-1beta (IL-1beta)-converting enzyme. This results in the killing of defense cells and in the release of IL-1beta. In vivo, bacteria translocate through the epithelial barrier, essentially via M cells of the follicle-associated epithelium in the colonic and rectal mucosa. Apoptotic death of macrophages in subepithelial tissues allows bacterial survival and triggers inflammation, which destabilizes epithelial structures and facilitates further bacterial entry. Once they are intracellular, bacteria multiply within the cytoplasm and move from cell to cell by an actin-dependent process.  (+info)

Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide from Shigella dysenteriae type 1. (5/739)

Our development of vaccines to prevent shigellosis is based on the hypothesis that a critical (protective) level of serum IgG to the O-specific polysaccharide (O-SP) domain of Shigella lipopolysaccharide (LPS) confers immunity. The O-SP is a hapten and must be conjugated to a protein to induce serum antibodies. The O-SP of Shigella dysenteriae type 1 (approximately 27 tetrasaccharide repeat units), prepared by acid hydrolysis of the LPS, was bound to human serum albumin (HSA) by multiple point attachment (O-SP-HSA): The molar ratio of HSA to O-SP was 1.0. Synthetic saccharides, composed of one or multiples of the O-SP tetrasaccharide, equipped with a spacer at their reducing end, were bound to HSA by a single point attachment: The average molar ratios of the saccharides to HSA ranged from 4 to 24. Serum IgG anti-LPS, elicited in mice by O-SP-HSA or synthetic tetra-, octa-, dodeca-, and hexadecasaccharide fragments, was measured by ELISA. Outbred 6-week-old female mice were injected s.c. three times at biweekly intervals with 2.5 micrograms of saccharide as a conjugate and were bled 7 days after the second and third injections. Excepting the tetramer, conjugates of the octamer, dodecamer and hexadecamer elicited IgG LPS antibodies after the second injection, a statistically significant rise (booster) after the third injection, and higher levels than those vaccinated with O-SP-HSA (P = 0.0001). The highest geometric mean levels of IgG anti-LPS were elicited by the hexadecamer with 9 chains or 9 moles of saccharide/HSA (15.5 ELISA units) followed by the octamer with 20 chains (11.1 ELISA units) and the dodecamer with 10 chains (9.52 ELISA units). Clinical evaluation of these synthetic saccharides bound to a medically useful carrier is planned.  (+info)

Outbreaks of Shigella sonnei infection associated with eating fresh parsley--United States and Canada, July-August 1998. (6/739)

In August 1998, the Minnesota Department of Health reported to CDC two restaurant-associated outbreaks of Shigella sonnei infections. Isolates from both outbreaks had two closely related pulsed-field gel electrophoresis (PFGE) patterns that differed only by a single band. Epidemiologic investigations implicated chopped, uncooked, curly parsley as the common vehicle for these outbreaks. Through inquiries to health departments and public health laboratories, six similar outbreaks were identified during July-August (in California [two], Massachusetts, and Florida in the United States and in Ontario and Alberta in Canada). Isolates from five of these outbreaks had the same PFGE pattern identified in the two outbreaks in Minnesota. This report describes the epidemiologic, traceback, environmental, and laboratory investigations, which implicated parsley imported from a farm in Mexico as the source of these outbreaks.  (+info)

Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children. (7/739)

O-specific polysaccharide conjugates of shigellae were safe and immunogenic in young adults, and a Shigella sonnei conjugate conferred protection [1-3]. Shigellosis is primarily a disease of children; therefore, the safety and immunogenicity of S. sonnei and Shigella flexneri 2a conjugates were studied in 4- to 7-year-old children. Local and systemic reactions were minimal. The first injection of both conjugates elicited significant rises in geometric mean levels of serum IgG only to the homologous lipopolysaccharide (LPS) (S. sonnei, 0.32-8.25 ELISA units [EU]; S. flexneri 2a, 1.15-20.5 EU; P<.0001). Revaccination at 6 weeks induced a booster response to S. flexneri 2a LPS (20.5-30.5 EU, P=.003). Six months later, the geometric mean levels of IgG anti-LPS for both groups were higher than the prevaccination levels (P<.0001). Similar, but lesser, rises were observed for IgM and IgA anti-LPS. The investigational Shigella conjugates were safe and immunogenic in children and merit evaluation of their efficacy.  (+info)

A functional role for ezrin during Shigella flexneri entry into epithelial cells. (8/739)

Shigella flexneri is an enteroinvasive bacterium responsible for bacillary dysentery in humans. Bacterial entry into epithelial cells is a crucial step for the establishment of the infection. It is characterized by a transient reorganization of the host cell cytoskeleton at the site of bacterial interaction with the cell membrane, which leads to bacterial engulfment by a macropinocytic process. We show in this study that the membrane-cytoskeleton linker, ezrin, a member of the ERM (ezrin, radixin, moesin) family, plays an active role in the process of Shigella uptake. Ezrin is highly enriched in cellular protrusions induced by the bacterium and is found in close association with the plasma membrane. In addition, Shigella entry is significantly reduced in cells transfected with a dominant negative allele of ezrin with entry foci showing much shorter cellular protrusions. These results indicate that ezrin not only acts as a membrane-cytoskeleton linker, but may also mediate extension of cellular projections in the presence of signals such as those elicited by invading microorganisms.  (+info)