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

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

Author information

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

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.

PMID:
18264109
DOI:
10.1038/nm1720
[Indexed for MEDLINE]

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