St Leger Anthony J, Desai Jigar V, Drummond Rebecca A, Kugadas Abirami, Almaghrabi Fatimah, Silver Phyllis, Raychaudhuri Kumarkrishna, Gadjeva Mihaela, Iwakura Yoichiro, Lionakis Michail S, Caspi Rachel R
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
Fungal Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Immunity. 2017 Jul 18;47(1):148-158.e5. doi: 10.1016/j.immuni.2017.06.014. Epub 2017 Jul 11.
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 γδ 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.
肠道、口腔、鼻咽和阴道等黏膜部位都有相关的共生菌群。眼睛表面也是一个黏膜部位，但仍难以证明存在有活性的常驻眼部微生物群。在这里，我们使用眼表疾病小鼠模型来揭示共生菌存在于眼黏膜中，并具有功能性免疫后果。我们分离出了一种这样的候选共生菌——乳房棒状杆菌，并表明这种微生物在眼黏膜中引发了γδT细胞产生共生菌特异性白细胞介素-17反应，这对局部免疫至关重要。这种共生菌特异性反应促使中性粒细胞募集，并将抗菌物质释放到眼泪中，从而保护眼睛免受致病性白色念珠菌或铜绿假单胞菌感染。我们的研究结果提供了直接证据，证明眼表面存在常驻共生微生物群，并确定了其影响眼部免疫稳态和宿主防御的细胞机制。
