Interleukin-22 regulates the complement system to promote resistance against pathobionts after pathogen-induced intestinal damage.
|
| Abstract |
Pathobionts play a critical role in disease development, but the immune mechanisms against pathobionts remain poorly understood. Here, we report a critical role for interleukin-22 (IL-22) in systemic protection against bacterial pathobionts that translocate into the circulation after infection with the pathogen Clostridium difficile. Infection with C. difficile induced IL-22, and infected Il22(-/-) mice harbored high numbers of pathobionts in extraintestinal organs despite comparable pathogen load and intestinal damage in mutant and wild-type mice. Pathobionts exhibited increased resistant against complement-mediated phagocytosis, and their intravenous administration resulted in high animal mortality. Selective removal of translocated commensals rescued Il22(-/-) mice, and IL-22 administration enhanced the elimination of pathobionts. Mechanistically, IL-22 augmented bacterial phagocytosis by increasing the expression and bacterial binding of complement C3. Our study demonstrates an unexpected role for IL-22 in controlling the elimination of pathobionts that enter the systemic circulation through the regulation of the complement system.
|
|---|---|
| Authors | Mizuho Hasegawa, Shoko Yada, Meng Zhen Liu, Nobuhiko Kamada, Raúl Muñoz-Planillo, Nhu Do, Gabriel Núñez, Naohiro Inohara |
| Journal | Immunity (Immunity) Vol. 41 Issue 4 Pg. 620-32 (Oct 16 2014) ISSN: 1097-4180 [Electronic] United States |
| PMID | 25367575 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!