title: Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection.
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(-/-) (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.
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: abtm@mskcc.org.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Abt
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Brittany B
authors.initials: BB
authors.lastname: Lewis
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Caballero
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Carter
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Bože
authors.initials: B
authors.lastname: Sušac
authors.affiliation: Lucille Castori Center for Microbes Inflammation and Cancer, Molecular Microbiology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Lilan
authors.initials: L
authors.lastname: Ling
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Leiner
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Lucille Castori Center for Microbes Inflammation and Cancer, Molecular Microbiology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: pamere@mskcc.org.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology*; D060467:Disease Resistance; D007113:Immunity, Innate; D016131:Lymphocyte Subsets / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016019:Survival Analysis