Recovery from acute C. difficile infection is independent of adaptive immunity
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Lack of innate lymphoid cells leads to mortality following C. difficile infection
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Transfer of ILCs into susceptible hosts restores protection against C. difficile
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Type-1 ILCs mediate IFN-γ-dependent protection against C. difficile
Summary
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.