Why does the healthy cornea resist Pseudomonas aeruginosa infection?
Why does the healthy cornea resist Pseudomonas aeruginosa infection?
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DOI：
10.1016/j.ajo.2013.03.001
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发表时间：
2013-06
影响因子：
4.2
通讯作者：
Fleiszig SM
中科院分区：
文献类型：
--
作者：
Evans DJ;Fleiszig SM
根据我们对铜绿假单胞菌的研究结果，提供我们对角膜抗感染原因的看法。我们专注于我们目前对细菌，泪液和角膜上皮细胞之间的相互作用的理解，这些相互作用决定了健康作为通常的结果，并提出了一个理论模型，用于隐形透镜佩戴如何改变这些相互作用，使铜绿假单胞菌感染的易感性。使用“空感染”体内模型、培养的人角膜上皮细胞、戴隐形眼镜的动物模型和细菌遗传学有助于阐明铜绿假单胞菌在眼表存活、粘附和穿过多层角膜上皮的机制。这些模型也有助于阐明角膜上皮先天防御的分子机制。泪液和角膜上皮联合收割机对角膜的铜绿假单胞菌感染形成强大的防御。这种防御的一部分涉及抗微生物剂的表达，如β-防御素、凯萨林菌素LL-37、细胞角蛋白衍生的抗微生物肽和RNA酶7。免疫调节剂如SP-D和ST 2也有作用。角膜的先天防御部分依赖于MyD 88，这是TLR和IL-1 R信号传导的关键衔接蛋白，但基底层代表了细菌渗透的最终屏障。克服这些防御涉及铜绿假单胞菌适应、第三型分泌系统的表达、蛋白酶和隐形眼镜上的铜绿假单胞菌生物膜形成。经过20多年的研究，重点是了解接触透镜佩戴如何易患铜绿假单胞菌感染，我们的工作假设将微生物角膜炎归咎于细菌对眼表防御的适应，以及由于透镜下角膜捕获细菌和泪液而引起的角膜表面生物化学变化。
To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas aeruginosa. We focus on our current understanding of the interplay between bacteria, tear fluid and the corneal epithelium that determine health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P. aeruginosa infection. Use of “null-infection” in vivo models, cultured human corneal epithelial cells, contact lens-wearing animal models, and bacterial genetics help to elucidate mechanisms by which P. aeruginosa survive at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense. Tear fluid and the corneal epithelium combine to make a formidable defense against P. aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P. aeruginosa adaptation, expression of the type three secretion system, proteases, and P. aeruginosa biofilm formation on contact lenses. After more than two decades of research focused on understanding how contact lens wear predisposes to P. aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens.
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