Innate immune defenses mediated by two ilc subsets are critical for protection against acute clostridium difficile infection

  • Abt M
  • Lewis B
  • Caballero S
 et al. 
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Abstract

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-/- (Raggc-/-) mice (which additionally lack ILCs) with C. difficile. In contrast to Rag1-/- mice, ILC-deficient Raggc-/- mice rapidly succumbed to infection. Rag1-/- but not Raggc-/- mice upregulate expression of ILC1- or ILC3-associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Raggc-/- mice. While ILC3s made a minor contribution to resistance, loss of IFN-g or T-betexpressing ILC1s in Rag1-/- mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile.

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Authors

  • Michael C. Abt

  • Brittany B. Lewis

  • Silvia Caballero

  • Huizhong Xiong

  • Rebecca A. Carter

  • Boze Susac

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