An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells

被引:205
作者
St Leger, Anthony J. [1 ]
Desai, Jigar V. [2 ]
Drummond, Rebecca A. [2 ]
Kugadas, Abirami [3 ]
Almaghrabi, Fatimah [1 ]
Silver, Phyllis [1 ]
Raychaudhuri, Kumarkrishna [1 ]
Gadjeva, Mihaela [3 ]
Iwakura, Yoichiro [4 ]
Lionakis, Michail S. [2 ]
Caspi, Rachel R. [1 ]
机构
[1] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA
[2] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA USA
[4] Tokyo Univ Sci, Inst Med Sci, Ctr Expt Anim Models, Tokyo, Japan
关键词
LYMPHOID-TISSUE; CANDIDA-ALBICANS; MICROBIOME; DISEASE; SKIN; INFLAMMATION; RESISTANCE; DIVERSITY; KERATITIS; BACTERIA;
D O I
10.1016/j.immuni.2017.06.014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mucosal sites such as the intestine, oral cavity, nasopharynx, and vagina all have associated commensal flora. The surface of the eye is also a mucosal site, but proof of a living, resident ocular microbiome remains elusive. Here, we used a mouse model of ocular surface disease to reveal that commensals were present in the ocular mucosa and had functional immunological consequences. We isolated one such candidate commensal, Corynebacterium mastitidis, and showed that this organism elicited a commensal-specific interleukin-17 response from gamma delta T cells in the ocular mucosa that was central to local immunity. The commensal-specific response drove neutrophil recruitment and the release of antimicrobials into the tears and protected the eye from pathogenic Candida albicans or Pseudomonas aeruginosa infection. Our findings provide direct evidence that a resident commensal microbiome exists on the ocular surface and identify the cellular mechanisms underlying its effects on ocular immune homeostasis and host defense.
引用
收藏
页码:148 / +
页数:16
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