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Contribution of Flagellin Pattern Recognition to Intestinal Inflammation during Salmonella enterica Serotype Typhimurium Infection

2009; American Society for Microbiology; Volume: 77; Issue: 5 Linguagem: Inglês

10.1128/iai.01341-08

1098-5522

Sebastian Winter, Parameth Thiennimitr, Sean‐Paul Nuccio, Takeshi Haneda, Maria G. Winter, R. Paul Wilson, Joseph M. Russell, Thomas Henry, Quynh T. Tran, Sara D. Lawhon, Gabriel Gomez, Charles Bevins, Holger Rüssmann, Denise M. Monack, L. Garry Adams, Andreas J. Bäumler,

Immune Response and Inflammation

ABSTRACT Salmonella enterica serotype Typhimurium causes acute inflammatory diarrhea in humans. Flagella contribute to intestinal inflammation, but the mechanism remains unclear since most mutations abrogating pattern recognition of flagellin also prevent motility and reduce bacterial invasion. To determine the contribution of flagellin pattern recognition to the generation of innate immune responses, we compared in two animal models a nonmotile, but flagellin-expressing and -secreting serotype Typhimurium strain ( flgK mutant) to a nonmotile, non-flagellin-expressing strain ( flgK fliC fljB mutant). In vitro, caspase-1 can be activated by cytosolic delivery of flagellin, resulting in release of the interferon gamma inducing factor interleukin-18 (IL-18). Experiments with streptomycin-pretreated caspase-1-deficient mice suggested that induction of gamma interferon expression in the murine cecum early (12 h) after serotype Typhimurium infection was caspase-1 dependent but independent of flagellin pattern recognition. In addition, mRNA levels of the CXC chemokines macrophage inflammatory protein 2 and keratinocyte-derived chemokine were markedly increased early after serotype Typhimurium infection of streptomycin-pretreated wild-type mice regardless of flagellin expression. In contrast, in bovine ligated ileal loops, flagellin pattern recognition contributed to increased mRNA levels of macrophage inflammatory protein 3α and more fluid accumulation at 2 h after infection. Collectively, our data suggest that pattern recognition of flagellin contributes to early innate host responses in the bovine ileal mucosa but not in the murine cecal mucosa.