A Novel Innate Response of Human Corneal Epithelium to Heat-killed Candida albicans by Producing Peptidoglycan Recognition Proteins.
A Novel Innate Response of Human Corneal Epithelium to Heat-killed Candida albicans by Producing Peptidoglycan Recognition Proteins.
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人角膜上皮通过产生肽聚糖识别蛋白对热灭活的白色念珠菌产生新的先天反应
DOI：
10.1371/journal.pone.0128039
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li DQ
中科院分区：
文献类型：
--
作者：
Hua X;Yuan X;Li Z;Coursey TG;Pflugfelder SC;Li DQ
真菌感染的角膜可以威胁视力，并有一个更坏的预后比其他类型的微生物角膜感染。表达于眼表的肽聚糖识别蛋白（PGLYRP）通过激活Toll样受体（TLR）或增加吞噬作用在针对细菌性角膜感染的免疫应答中起重要作用。然而，PGLYRPs在对真菌病原体的先天免疫应答中的作用尚未研究。在这项研究中，我们观察到暴露于活的或热灭活的白色念珠菌（HKCA）的原代人角膜上皮细胞（HCEC）中三种PGLYRP 2-4的显着诱导。C型凝集素受体dectin-1通过促进巨噬细胞和树突状细胞的吞噬活性和细胞因子产生在控制白色念珠菌感染中起关键作用。在这里，我们证明了dectin-1由正常人角膜组织和原代HCEC表达。HKCA暴露在mRNA和蛋白水平上增加HCECs上dectin-1的表达。有趣的是，dectin-1中和抗体、IκB-α抑制剂BAY 11 -7082和NF-κB活化抑制剂喹唑啉阻断了HCEC中NF-κB p65核转位以及HKCA诱导的PGLYRPs。此外，rhPGLYRP-2被发现在体外抑制白色念珠菌的菌落形成单位。结论：dectin-1在人角膜上皮细胞中表达，dectin-1/NF-κB信号通路在白念珠菌/HKCA诱导的人角膜上皮细胞PGLYRP分泌中起重要调节作用。
Fungal infections of the cornea can be sight-threatening and have a worse prognosis than other types of microbial corneal infections. Peptidoglycan recognition proteins (PGLYRP), which are expressed on the ocular surface, play an important role in the immune response against bacterial corneal infections by activating toll-like receptors (TLRs) or increasing phagocytosis. However, the role of PGLYRPs in innate immune response to fungal pathogens has not been investigated. In this study, we observed a significant induction of three PGLYRPs 2–4 in primary human corneal epithelial cells (HCECs) exposed to live or heat-killed Candida albicans (HKCA). The C-type lectin receptor dectin-1 plays a critical role in controlling Candida albicans infections by promoting phagocytic activity and cytokine production in macrophages and dendritic cells. Here, we demonstrate that dectin-1 is expressed by normal human corneal tissue and primary HCECs. HKCA exposure increased expression of dectin-1 on HCECs at mRNA and protein levels. Interestingly, dectin-1 neutralizing antibody, IκB-α inhibitor BAY11-7082, and NF-κB activation inhibitor quinazoline blocked NF-κB p65 nuclear translocation, as well as the induction of the PGLYRPs by HKCA in HCECs. Furthermore, rhPGLYRP-2 was found to suppress colony-forming units of Candida albicans in vitro. In conclusion, these findings demonstrate that dectin-1 is expressed by human corneal epithelial cells, and dectin-1/NF-κB signaling pathway plays an important role in regulating Candida albicans/HKCA-induced PGLYRP secretion by HCECs.
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影响因子：
3.6
作者：
Dziarski, R
通讯作者：
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4.8
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