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Recombinant IL-22 promotes protection in a murine model of Aspergillus flavus keratitis and mediates host immune responses in human corneal epithelial cells
Cellular Microbiology ( IF 3.4 ) Pub Date : 2021-05-24 , DOI: 10.1111/cmi.13367
Lakshmi Sruthi Mallela 1 , Prerana Sharma 1, 2 , Tata Santosh RamaBhadra Rao 1 , Sanhita Roy 1
Affiliation  

Aspergillus flavus is a leading cause of corneal infections in India and worldwide, resulting in severe visual impairment. We studied the host immune response towards A. flavus in immortalised human corneal epithelial cells (HCEC) and found increased expression of Toll-like receptors, antimicrobial peptides and proinflammatory cytokines like IL-6 and IL-8. Differential expressions of antimicrobial peptides were determined in corneal scrapings from A. flavus keratitis patients with significantly increased expression of LL-37, S100A12 and RNase 7. Increased levels of IL-22 expression were observed both in patients with A. flavus keratitis and in experimental mice model of corneal infections along with IL-17, IL-23 and IL-18. IL-22 is an important mediator of inflammation during microbial infections, and acts primarily on fibroblasts and epithelial cells. We observed constitutive expression of IL-22 receptors in HCEC, and IL-22 mediated activation of NF-κB, MAPK pathways and STAT3, along with increased expression of antimicrobial peptides in these cells. IL-22 also efficiently lessened cell deaths in corneal epithelial cells during A. flavus infection in vitro. Furthermore, recombinant IL-22 reduced fungal burden and corneal opacity in an experimental murine model of A. flavus keratitis.

中文翻译:

重组 IL-22 在黄曲霉角膜炎小鼠模型中促进保护并在人角膜上皮细胞中介导宿主免疫反应

黄曲霉是印度和世界范围内角膜感染的主要原因,导致严重的视力障碍。我们研究了永生化人角膜上皮细胞 (HCEC) 中对黄曲霉的宿主免疫反应,发现 Toll 样受体、抗菌肽和促炎细胞因子如 IL-6 和 IL-8 的表达增加。在黄曲霉角膜炎患者的角膜刮片中测定了抗菌肽的差异表达,LL-37、S100A12 和 RNase 7 的表达显着增加。在黄曲霉患者中均观察到 IL-22 表达水平增加角膜炎和角膜感染的实验小鼠模型以及 IL-17、IL-23 和 IL-18。IL-22 是微生物感染期间炎症的重要介质,主要作用于成纤维细胞和上皮细胞。我们观察到 HCEC 中 IL-22 受体的组成型表达,以及 IL-22 介导的 NF-κB、MAPK 通路和 STAT3 的激活,以及这些细胞中抗菌肽的表达增加。在体外黄曲霉感染期间,IL-22 还有效地减少了角膜上皮细胞中的细胞死亡。此外,重组 IL-22 减少了A. flavus角膜炎实验鼠模型中的真菌负荷和角膜混浊。
更新日期:2021-05-24
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