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Cell Host Microbe. 2015 Jul 8;18(1):27-37. doi: 10.1016/j.chom.2015.06.011.

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

Author information

1
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: abtm@mskcc.org.
2
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
3
Lucille Castori Center for Microbes Inflammation and Cancer, Molecular Microbiology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4
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.

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.

PMID:
26159718
PMCID:
PMC4537644
DOI:
10.1016/j.chom.2015.06.011
[Indexed for MEDLINE]
Free PMC Article

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