Contribution of flagellin pattern recognition to intestinal inflammation during Salmonella enterica serotype Typhimurium infection

Sebastian E. 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 L Bevins, Holger Rüssmann, Denise M. Monack, L. Garry Adams, Andreas J Baumler

Research output: Contribution to journalArticle

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1904-1916
Number of pages13
JournalInfection and Immunity
Volume77
Issue number5
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

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    Winter, S. E., Thiennimitr, P., Nuccio, S. P., Haneda, T., Winter, M. G., Wilson, R. P., Russell, J. M., Henry, T., Tran, Q. T., Lawhon, S. D., Gomez, G., Bevins, C. L., Rüssmann, H., Monack, D. M., Adams, L. G., & Baumler, A. J. (2009). Contribution of flagellin pattern recognition to intestinal inflammation during Salmonella enterica serotype Typhimurium infection. Infection and Immunity, 77(5), 1904-1916. https://doi.org/10.1128/IAI.01341-08