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

被引：259

作者：

Abt, Michael C. ^{[1
]}

Lewis, Brittany B. ^{[1
]}

Caballero, Silvia ^{[1
]}

Xiong, Huizhong ^{[1
]}

Carter, Rebecca A. ^{[1
]}

Susac, Boze ^{[1
]}

Ling, Lilan ^{[2
]}

Leiner, Ingrid ^{[1
]}

Pamer, Eric G. ^{[1
,2
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Program Immunol, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Mol Microbiol Core Facil, Lucille Castori Ctr Microbes Inflammat & Canc, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Med, Infect Dis Serv, New York, NY 10065 USA

来源：

CELL HOST & MICROBE | 2015年 / 18卷 / 01期

关键词：

LYMPHOID-CELLS; NEUTROPHIL RECRUITMENT; T-BET; INTESTINAL MICROBIOTA; HOST-DEFENSE; GAMMA; MICE; INTERLEUKIN-22; TRANSMISSION; INTERFERON;

D O I：

10.1016/j.chom.2015.06.011

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

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(-/-) (Rag gamma c(-/-)) mice (which additionally lack ILCs) with C. difficile. In contrast to Rag1(-/-) mice, ILC-deficient Rag gamma c(-/-) mice rapidly succumbed to infection. Rag1(-/-) but not Rag gamma c(-/-) mice upregulate expression of ILC1-or ILC3-associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Rag gamma c(-/-) mice. While ILC3s made a minor contribution to resistance, loss of IFN-gamma 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.

引用

页码：27 / 37

页数：11

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