Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Author: ["Yan Zheng","Patricia A Valdez","Dimitry M Danilenko","Yan Hu","Susan M Sa","Qian Gong","Alexander R Abbas","Zora Modrusan","Nico Ghilardi","Frederic J de Sauvage","Wenjun Ouyang"]
Publication: Nature Medicine
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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 RegIIIβ and RegIIIγ, in colonic epithelial cells. Exogenous mouse or human RegIIIγ 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.
Cite this article
Zheng, Y., Valdez, P., Danilenko, D. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14, 282–289 (2008). https://doi.org/10.1038/nm1720
