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.
Zheng
Yan
Y
Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
Valdez
Patricia A
PA
Danilenko
Dimitry M
DM
Hu
Yan
Y
Sa
Susan M
SM
Gong
Qian
Q
Abbas
Alexander R
AR
Modrusan
Zora
Z
Ghilardi
Nico
N
de Sauvage
Frederic J
FJ
Ouyang
Wenjun
W
D000818:Animals; D001422:Bacterial Adhesion; D044082:Citrobacter rodentium / Q000276:immunology*; D003106:Colon / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology*; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D000097043:Interleukin-22
D003546:Cysteine Endopeptidases; D053759:Interleukin-23; D007378:Interleukins; D000097043:Interleukin-22