The Blessings and Curses of Intestinal Inflammation

Winter, Sebastian; Keestra, A. Marijke; Tsolis, Renée M.; Bäumler, Andreas J.

doi:10.1016/j.chom.2010.06.003

Cited by 43 publications

(42 citation statements)

References 69 publications

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“…Detection of the lipopolysaccharide (LPS) O antigen of Gram-negative bacteria by C3 is a pattern recognition event that initiates the alternative pathway of complement activation (9,38). During the initial steps of this pathway, C3b, a cleavage products of C3, binds covalently to hydroxyl groups present in LPS, a process known as C3 fixation.…”

Section: Resultsmentioning

confidence: 99%

“…Complement, specifically C3, senses conserved microbial structures, such as LPS of Gram-negative bacteria, which represents an important pattern recognition event in the detection of microbes by the innate immune system (9,38). Complement activation results in the fixation of C3b on the bacterial surface, because this C3 cleavage product contains a reactive thioester group which forms esters with free hydroxyl groups of sugars (31).…”

Section: Discussionmentioning

confidence: 99%

“…One arm of the innate immune system involved in detection of invasive microbes is the complement system (9,38). Complement deposition on the bacterial cell surface and opsonophagocytosis can be prevented by capsular polysaccharides of invasive Gramnegative pathogens, including Neisseria meningitidis, Klebsiella pneumoniae, and Escherichia coli isolates associated with extraintestinal infections (1,15,16,35).…”

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confidence: 99%

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The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi

et al. 2011

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Salmonella enterica serotype Typhi (S. Typhi) causes an estimated 21 million annual cases of typhoid fever, a severe systemic infection resulting in 200,000 to 600,000 fatalities per year (5, 37). After ingestion, S. Typhi invades the intestinal mucosa, but symptoms develop only after an average incubation period of 2 weeks (23). The relatively long incubation period of typhoid fever suggests that S. Typhi can evade or suppress detection by the innate immune system during the initial stages of infection (26,28,33). However, the virulence mechanisms that enable S. Typhi to evade components of the innate immune system early after infection have long remained elusive.One arm of the innate immune system involved in detection of invasive microbes is the complement system (9, 38). Complement deposition on the bacterial cell surface and opsonophagocytosis can be prevented by capsular polysaccharides of invasive Gramnegative pathogens, including Neisseria meningitidis, Klebsiella pneumoniae, and Escherichia coli isolates associated with extraintestinal infections (1,15,16,35). S. Typhi produces the virulence (Vi) capsular polysaccharide (8), which is encoded by the viaB locus (17). The viaB locus is a 14-kb DNA region containing genes required for the regulation (tviA), the biosynthesis (tviBCDE), and the export (vexABCDE) of the Vi capsular polysaccharide (36). In S. Typhi, the role of the Vi capsular polysaccharide in reducing complement deposition has not been convincingly demonstrated. The viaB locus of S. Typhi is located on a 134-kb DNA region, termed Salmonella pathogenicity island 7 (SPI-7) (24). SPI-7 is genetically unstable and can be lost upon laboratory passage (3,22). Clinical S. Typhi isolates expressing the Vi capsular polysaccharide tend to bind less complement on their surface in vitro than clinical isolates lacking capsule expression (20). While this report concludes that the Vi capsular polysaccharide inhibits opsonophagocytosis, the evidence is not conclusive, because it is based on comparison of nonisogenic, clinical S. Typhi isolates. Genetic differences between these clinical isolates were not defined but likely included the entire SPI-7 region. Additionally, the in vivo relevance of phenotypes attributed to the Vi capsular polysaccharide remains to be established using animal models.With the exception of higher primates, vertebrate hosts are resistant to infection with the human-adapted S. Typhi, which has prevented the use of animal models to investigate the in vivo relevance of results obtained using tissue culture. While mice orally inoculated with S. Typhi are not suited to study the development of typhoid fever, we reasoned that this animal model could be used for studying isolated steps during infection, provided that the relevant interactions were not species specific. Here we investigated the role of the Vi capsular polysaccharide on complement-mediated phagocytosis and its impact on bacterial clearance during an infection. MATERIALS AND METHODSBacterial strains and culture conditions. Vi...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi

et al. 2011

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“…Histopathological analysis of the cecal mucosa after S. Typhimurium infection. C57BL/6 mice (wild type), MyD88-deficient mice, IL-17 receptor-deficient mice, or IL-1 receptor-deficient mice were inoculated with wild-type S. Typhimurium, a noninvasive S. Typhimurium mutant (ZA21), or sterile medium (Mock infection), and the cecum was collected 48 h after infection for histopathological analysis (Table 1) such as lipopolysaccharide (42). The resulting activation of complement through the alternative pathway generates the complement fragments C3a and C5a, which are potent inducers of inflammatory responses (11).…”

Section: Vol 79 2011mentioning

confidence: 99%

Early MyD88-Dependent Induction of Interleukin-17A Expression during Salmonella Colitis

et al. 2011

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“…As the receptor lacks a ligand-binding leucine-rich repeat domain, elucidating the function of the C-terminal B30.2 domain, which has been reported to bind actin and to facilitate co-localization with the cytoskeleton [7], will likely shed light on Pyrin's activation mechanism. Also, it will also be interesting to investigate whether certain pathogenic bacteria intentionally activate Pyrinmediated inflammatory responses to provide a competitive advantage over resident commensals, as has been described for the inflammation induced during S. Typhimurium infection [8]. Finally, while a previous report has described that TcdB toxin from C. difficile activated an unknown inflammasome [9], this study showed that the enzymatic activity of TcdB was dispensable.…”

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confidence: 46%