Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens

Nat Med. 2008 Mar;14(3):282-9. doi: 10.1038/nm1720. Epub 2008 Feb 10.

Abstract

Infections by attaching and effacing (A/E) bacterial pathogens, such as Escherichia coli O157:H7, pose a serious threat to public health. Using a mouse A/E pathogen, Citrobacter rodentium, we show that interleukin-22 (IL-22) has a crucial role in the early phase of host defense against C. rodentium. Infection of IL-22 knockout mice results in increased intestinal epithelial damage, systemic bacterial burden and mortality. We also find that IL-23 is required for the early induction of IL-22 during C. rodentium infection, and adaptive immunity is not essential for the protective role of IL-22 in this model. Instead, IL-22 is required for the direct induction of the Reg family of antimicrobial proteins, including RegIIIbeta and RegIIIgamma, in colonic epithelial cells. Exogenous mouse or human RegIIIgamma substantially improves survival of IL-22 knockout mice after C. rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens.

MeSH terms

  • Animals
  • Bacterial Adhesion*
  • Citrobacter rodentium / immunology*
  • Colon / metabolism
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology*
  • Gene Expression Regulation
  • Immunity, Innate / immunology
  • Interleukin-23 / genetics
  • Interleukin-23 / metabolism
  • Interleukins / biosynthesis
  • Interleukins / deficiency
  • Interleukins / genetics
  • Interleukins / immunology*
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Time Factors

Substances

  • Interleukin-23
  • Interleukins
  • Cysteine Endopeptidases
  • interleukin-22

Associated data

  • GEO/GSE10010