Article abstract
Nature Medicine 14, 282 - 289 (2008)
Published online: 10 February 2008 | doi:10.1038/nm1720
Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens
Yan Zheng1,5, Patricia A Valdez1, Dimitry M Danilenko2, Yan Hu1, Susan M Sa2, Qian Gong1, Alexander R Abbas3, Zora Modrusan4, Nico Ghilardi4, Frederic J de Sauvage4 & Wenjun Ouyang1
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 RegIII
and RegIII
, in colonic epithelial cells. Exogenous mouse or human RegIII 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.
- Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
- Department of Pathology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
- Department of Bioinformatics, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
- Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
- Current address: Inflammation Pathways Group, Pfizer Global Research & Development, St. Louis Laboratories, 700 Chesterfield Parkway West, Chesterfield, Missouri 63017, USA.
Correspondence to: Wenjun Ouyang1 e-mail: ouyang.wenjun@gene.com