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黄曲霉菌和白念珠菌感染人视网膜色素上皮细胞的差异炎症反应:在眼内炎治疗中的作用。

Differential inflammatory response to Aspergillus flavus and Candida albicans infection in human retinal pigment epithelial cells: Role in treatment of endophthalmitis.

机构信息

Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana 500034 , India; Manipal Academy of Higher Education, Karnataka, India.

Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana 500034 , India.

出版信息

J Mycol Med. 2021 Sep;31(3):101136. doi: 10.1016/j.mycmed.2021.101136. Epub 2021 Apr 3.

Abstract

OBJECTIVE

Fungal endophthalmitis is an emerging vision-threatening complication in tropical countries and the Retinal pigment epithelial cells (RPE) are said to play a major role in the retinal pathology. The aim of this study was to compare the immune response of Retinal pigment epithelial cells (RPE) challenged with A. flavus and C. albicans strains, isolated from patients with fungal endophthalmitis.

MATERIAL AND METHODS

Retinal Pigment epithelial cells (ARPE-19) cells were infected with A. flavus and C. albicans, and gene expression were assessed for TLRs, immune-mediators, and matrix metalloproteinases (MMPs).

RESULTS

We observed a time-dependent gene expression of TLRs (TLR-2,-7 and -9); IL-8 and TNF-α in RPE cells challenged with A. flavus and C. albicans. Additonally, IL-6 (3.3 fold), IL-10 (15.2 fold), and IL-17 (5.6 fold) were significantly up-regulated only in cells infected with A. flavus. Additionally, MMP-9 gene expression was up-regulated in both A.flavus as well as C.albicans infected cells, while MMP- 2 gene expression was induced only in cells infected with C.albicans. A total of 9 upregulated differential expression of genes (DEGs) in A. flavus infected cells and 7 DEGs in C. albicans infected cells were used to construct Protein-protein interaction (PPI) network.

CONCLUSION

RPE cells induced a differential innate immune response depending on fungal species involved (A.flavus and C.albicans) and may provide clues for novel treatment targets and better prognosis.

摘要

目的

真菌性眼内炎是热带国家一种新出现的威胁视力的并发症,视网膜色素上皮细胞(RPE)被认为在视网膜病变中起主要作用。本研究旨在比较从真菌性眼内炎患者中分离出的黄曲霉和白念珠菌菌株对视网膜色素上皮细胞(RPE)的免疫反应。

材料和方法

用 A. flavus 和 C. albicans 感染视网膜色素上皮细胞(ARPE-19)细胞,并评估 TLRs、免疫介质和基质金属蛋白酶(MMPs)的基因表达。

结果

我们观察到 RPE 细胞受到 A. flavus 和 C. albicans 挑战时 TLRs(TLR-2、-7 和 -9);IL-8 和 TNF-α的时间依赖性基因表达。此外,仅在感染 A. flavus 的细胞中,IL-6(3.3 倍)、IL-10(15.2 倍)和 IL-17(5.6 倍)显著上调。此外,MMP-9 基因表达在 A. flavus 和 C. albicans 感染的细胞中均上调,而 MMP-2 基因表达仅在感染 C. albicans 的细胞中上调。在感染 A. flavus 的细胞中有 9 个上调的差异表达基因(DEGs),在感染 C. albicans 的细胞中有 7 个 DEGs 用于构建蛋白质-蛋白质相互作用(PPI)网络。

结论

RPE 细胞根据涉及的真菌种类(A. flavus 和 C. albicans)诱导不同的先天免疫反应,这可能为新的治疗靶点和更好的预后提供线索。

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