Clostridium difficile, an opportunistic pathogen that infects the gastrointestinal tract following perturbation of the microbiota, damages the intestinal epithelium and can cause debilitating and potentially fatal colitis. Antibiotic treatment of C. difficile is often ineffective and whether innate immune defenses can be exploited to promote C. difficile clearance is unknown. Innate lymphoid cells (ILCs) are early responders to enteric infection, however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we compared C57BL/6, Rag1-/-, and Rag2-/- Il2rg-/- (Ragγc-/-) mice challenged with C. difficile. In contrast to C57BL/6 and Rag1-/- mice, ILC-deficient Ragγc-/- mice rapidly succumbed to infection. Protection against infection was restored by transferring ILCs into Ragγc-/- mice. While ILC3s made a minor contribution to resistance, loss of T-bet-expressing ILC1s or IFN-γ in Rag1-/- mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile.
Citation Format: Michael C. Abt, Brittany B. Lewis, Lilan Ling, Rebecca A. Carter, Boj Susac, Eric G. Pamer. Cooperative defense against acute Clostridium difficile infection is mediated by two innate lymphoid cell subsets. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A100.
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