Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis.
Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis.
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微生物群对铜绿假单胞菌诱导的角膜炎的抗性。
DOI：
10.1371/journal.ppat.1005855
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发表时间：
2016-09
期刊：
影响因子：
6.7
通讯作者：
Gadjeva M
中科院分区：
文献类型：
--
作者：
Kugadas A;Christiansen SH;Sankaranarayanan S;Surana NK;Gauguet S;Kunz R;Fichorova R;Vorup-Jensen T;Gadjeva M
眼部微生物区系的存在已有报道，但目前尚缺乏功能分析来评估其在调节眼部免疫方面的意义。我们比较了眼睛和肠道共生体在调节眼睛对铜绿假单胞菌引起的角膜炎的易感性方面的相对贡献。我们发现，在健康中，微生物群的存在通过显著增加泪膜中免疫效应物的浓度，包括分泌型IgA和补体蛋白，从而增强了眼睛的天然免疫屏障。与这一观点一致的是，通常对铜绿假单胞菌诱导的角膜炎具有抵抗力的瑞士韦氏(SW)小鼠由于缺乏微生物群而变得敏感。无菌(GF)小鼠的角膜细菌负荷增加和病理改变与常规维持的SW小鼠相比，就是例证。保护性免疫依赖于眼睛和肠道微生物区系，其中眼部微生物区系对感染的抵抗力有中等但显著的影响。与SPF对照组相比，感染GF组和抗生素治疗组小鼠的角膜IL-1？水平降低，且中和IL-1？增加了SPF组小鼠的眼部细菌负荷，因此这些事件是IL-1？凝固酶阴性葡萄球菌对GF小鼠的单克隆。从结膜拭子中分离出的细菌足以恢复对感染的抵抗力。总体而言，这些数据强调了微生物区系在调节眼部角膜炎易感性方面以前未被认识到的作用。我们预测，这些结果将对隐形眼镜佩戴者产生重大影响，在这种情况下，眼部共生群落的变化可能会使眼表容易受到感染。戴隐形眼镜与频繁的铜绿假单胞菌引起的角膜炎有关，然而这种联系的原因尚不清楚。最近基于基因组学的方法显示，与不戴隐形眼镜的人相比，戴隐形眼镜的人眼部共生群落发生了变化，这引发了重要的问题，即戴隐形眼镜是否会增加患者由于接触到皮肤来源的物种而发生角膜炎的频率，还是眼睛微生物群发挥了维持眼睛健康所需的免疫功能？我们展示了眼部微生物区系在调节对铜绿假单胞菌引起的感染的保护中的明确作用。在眼表，共生细菌提供信号，调节感染期间中性粒细胞募集的大小。这些事件可能是由常见的革兰氏阳性共生凝固酶阴性葡萄球菌(CNS)引起的。除了眼部微生物区系的影响外，肠道微生物区系还有一个重要的贡献，它刺激骨髓中中性粒细胞的发育，从而调节成熟中性粒细胞的池及其激活状态。总而言之，这些数据第一次显示了微生物区系在调节铜绿假单胞菌角膜炎易感性方面的作用。
The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa–induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice that are typically resistant to P. aeruginosa–induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found to be dependent on both eye and gut microbiota with the eye microbiota having a moderate, but significant impact on the resistance to infection. These events were IL-1ß–dependent as corneal IL-1ß levels were decreased in the infected GF and antibiotic-treated mice when compared to the SPF controls, and neutralization of IL-1ß increased the ocular bacterial burden in the SPF mice. Monocolonizing GF mice with Coagulase Negative Staphylococcus sp. isolated from the conjunctival swabs was sufficient to restore resistance to infection. Cumulatively, these data underline a previously unappreciated role for microbiota in regulating susceptibility to ocular keratitis. We predict that these results will have significant implications for contact lens wearers, where alterations in the ocular commensal communities may render the ocular surface vulnerable to infections. Contact lens wear is associated with frequent Pseudomonas aeruginosa–induced keratitis, however the reasons for this association remain unclear. Recent genomics–based approaches revealed that contact lens wearers harbor altered ocular commensal communities when compared to non-lens wearers raising important questions, namely, does wearing of contact lenses increase the frequency of keratitis in patients due to contamination of the contact lenses with species derived from the skin or does ocular microbiota exert immune functions that are required for the maintenance of ocular health? We demonstrate a clear role for ocular microbiota in regulating protection against Pseudomonas aeruginosa–induced infections. At the ocular surface, commensal bacteria provide signals that regulate the magnitude of neutrophil recruitment during infection. These events may be driven by a frequent gram-positive commensal–Coagulase Negative Staphylococcus (CNS) sp. In addition to the impact of ocular microbiota, there is an important contribution of gut microbiota that stimulate neutrophil development in the bone marrow, thereby regulating the pool of mature neutrophils and their activation state. Cumulatively, these data show for the first time a role for microbiota in regulating the susceptibility to P. aeruginosa–keratitis.
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影响因子：
4.2
作者：
Evans DJ;Fleiszig SM
通讯作者：
Fleiszig SM
DOI：
10.1038/nri3535
发表时间：
2013-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.1
作者：
Gauguet, Stefanie;D'Ortona, Samantha;Pier, Gerald B.
通讯作者：
Pier, Gerald B.
影响因子：
1.4
作者：
Hart, DE;Hosmer, M;Farris, RL
通讯作者：
Farris, RL
影响因子：
64.5
作者：
Chung H;Pamp SJ;Hill JA;Surana NK;Edelman SM;Troy EB;Reading NC;Villablanca EJ;Wang S;Mora JR;Umesaki Y;Mathis D;Benoist C;Relman DA;Kasper DL
通讯作者：
Kasper DL