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

Yan Zheng1, Patricia A Valdez, Dimitry M Danilenko

  • 1Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.

Nature Medicine
|February 12, 2008
PubMed

Insights

Interleukin-22 (IL-22) is vital for early host defense against attaching and effacing (A/E) bacterial pathogens. This cytokine promotes antimicrobial proteins, enhancing survival during infections like Citrobacter rodentium.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Attaching and effacing (A/E) bacterial pathogens, including Escherichia coli O157:H7, represent a significant public health concern.
  • Citrobacter rodentium serves as a mouse model for studying A/E pathogen infections and host immune responses.

Purpose of the Study:

  • To investigate the role of interleukin-22 (IL-22) in the early host defense against Citrobacter rodentium infection.
  • To elucidate the mechanisms by which IL-22 mediates protection against A/E bacterial pathogens.

Main Methods:

  • Utilized IL-22 knockout mice to assess the impact of IL-22 deficiency on C. rodentium infection outcomes.
  • Investigated the role of IL-23 in IL-22 induction during infection.
  • Examined the expression of Reg family antimicrobial proteins in response to IL-22.
  • Administered exogenous RegIIIgamma to IL-22 knockout mice to evaluate its protective effects.

Main Results:

  • IL-22 knockout mice exhibited exacerbated intestinal epithelial damage, increased systemic bacterial load, and higher mortality following C. rodentium infection.
  • IL-23 was essential for the early induction of IL-22 during C. rodentium infection.
  • IL-22's protective effect was independent of adaptive immunity in this model.
  • IL-22 directly induced Reg family antimicrobial proteins (RegIIIbeta and RegIIIgamma) in colonic epithelial cells.
  • Exogenous RegIIIgamma significantly improved survival in IL-22 knockout mice.

Conclusions:

  • IL-22 plays a critical role in the innate immune response during the early stages of A/E bacterial infections.
  • IL-22 mediates protection by inducing antimicrobial proteins like RegIIIgamma in the colonic epithelium.
  • This study identifies a novel innate immune function for IL-22 in combating A/E bacterial pathogens.

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