Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22

Infect Immun. 2017 Jan 26;85(2):e00806-16. doi: 10.1128/IAI.00806-16. Print 2017 Feb.

Abstract

Signaling through Toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine). We found that systemic administration of flagellin significantly increased the survival rate after intestinal infection (but not systemic infection) by Y. pseudotuberculosis This protection was associated with a low bacterial count in the gut and the spleen. In contrast, no protection was afforded by administration of the TLR4 agonist lipopolysaccharide, suggesting the presence of a flagellin-specific effect. Lastly, we found that TLR5- and MyD88-mediated signaling was required for the protective effects of flagellin, whereas neither lymphoid cells nor IL-22 was involved.

Keywords: TLR5; Toll-like receptors; Yersinia pseudotuberculosis; flagellin; interleukin-22; intestine; mouse infection.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Flagellin / administration & dosage
  • Flagellin / immunology*
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Knockout
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Toll-Like Receptors / metabolism
  • Yersinia pseudotuberculosis / immunology*
  • Yersinia pseudotuberculosis Infections / immunology*
  • Yersinia pseudotuberculosis Infections / metabolism*
  • Yersinia pseudotuberculosis Infections / microbiology
  • Yersinia pseudotuberculosis Infections / mortality

Substances

  • Interleukins
  • Lipopolysaccharides
  • Recombinant Fusion Proteins
  • Toll-Like Receptors
  • Flagellin