Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection

• Published in: Cell host & microbe 2015-07, Vol.18 (1), p.27-37
• Main Authors: Abt, Michael C., Lewis, Brittany B., Caballero, Silvia, Xiong, Huizhong, Carter, Rebecca A., Sušac, Bože, Ling, Lilan, Leiner, Ingrid, Pamer, Eric G.
• Format: Article
• Language: English
• Subjects: Animals; Clostridium difficile - immunology; Clostridium Infections - immunology; Disease Resistance; Immunity, Innate; Lymphocyte Subsets - immunology; Mice, Inbred C57BL; Mice, Knockout; Survival Analysis
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2015.06.011

Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment-induced gut microbiota perturbation. Innate lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1−/− (which lack T and B cells), and Rag2−/−Il2rg−/− (Ragγc−/−) mice (which additionally lack ILCs) with C. difficile. In contrast to Rag1−/− mice, ILC-deficient Ragγc−/− mice rapidly succumbed to infection. Rag1−/− but not Ragγc−/− mice upregulate expression of ILC1- or ILC3-associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Ragγc−/− mice. While ILC3s made a minor contribution to resistance, loss of IFN-γ or T-bet-expressing ILC1s in Rag1−/− mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile. [Display omitted] •Recovery from acute C. difficile infection is independent of adaptive immunity•Lack of innate lymphoid cells leads to mortality following C. difficile infection•Transfer of ILCs into susceptible hosts restores protection against C. difficile•Type-1 ILCs mediate IFN-γ-dependent protection against C. difficile C. difficile pathogenicity is determined by strain virulence, interactions with commensal bacteria, and the host’s inflammatory response to intestinal epithelial damage. Abt et al. demonstrate that type-1 and type-3 innate lymphoid cells function in concert and coordinate early host responses to provide initial resistance against C. difficile infection.