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

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.

Pubmed ID: 18264109

Authors

  • Zheng Y
  • Valdez PA
  • Danilenko DM
  • Hu Y
  • Sa SM
  • Gong Q
  • Abbas AR
  • Modrusan Z
  • Ghilardi N
  • de Sauvage FJ
  • Ouyang W

Journal

Nature medicine

Publication Data

March 7, 2008

Associated Grants

None

Mesh Terms

  • Animals
  • Bacterial Adhesion
  • Citrobacter rodentium
  • Colon
  • Cysteine Endopeptidases
  • Enterobacteriaceae Infections
  • Gene Expression Regulation
  • Immunity, Innate
  • Interleukin-23
  • Interleukins
  • Intestinal Mucosa
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Time Factors