Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, 250012, PR China; Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Jinan, 250012, PR China.
Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, 250012, PR China.
Exp Eye Res. 2021 Aug;209:108644. doi: 10.1016/j.exer.2021.108644. Epub 2021 May 31.
Fungal keratitis constitutes a serious vision-threatening disease. Toll-like receptors (TLRs) comprise key mediators of innate immunity triggered by Aspergillus fumigatus (AF) in the cornea, but the messenger between innate and adaptive immunity remained unknown. Thymic stromal lymphopoietin (TSLP) represents a critical factor of adaptive immunity. Here we investigated the expression of TSLP in corneal epithelial and stromal cells challenged by AF and its relationship with TLRs. We stimulated corneal cells with TLR ligands zymosan or lipopolysaccharide (LPS), human recombinant TSLP, or AF hyphae for various periods, with or without prior TLR2, TLR4, or TSLP inhibition. TLR2, TLR4, TSLP, IL-8, and TNF-α release and expression were measured via enzyme-linked immunosorbent analysis, quantitative polymerase chain reaction, or western blot. Corneal cell stimulation with zymosan or LPS induced up-regulated TSLP expression. Enhanced TSLP expression was associated with AF treatment in human corneal cells; TLR2 or TLR4 inhibition impaired the AF-induced TSLP levels. Human recombinant TSLP augmented TLR2 and TLR4 expression; RNA interference of TSLP attenuated TLR, IL-8, and TNF-α expression stimulated by AF hyphae. These findings indicated that TSLP participates in the immune response of corneal cells triggered by AF, which is closely related to TLR function, and the innate immunity mediated by TLRs could be enhanced by TSLP. Innate immunity may therefore transmit inflammatory signals to adaptive immunity through activation of TSLP; in turn, adaptive immunity likely exerts certain regulatory effects on innate immunity via TSLP. That is, TSLP could interact with innate immunity mediated by TLR2 and TLR4 in human corneal cells challenged by AF and thus may serve as a messenger between the innate and adaptive immune responses in AF keratitis.
真菌性角膜炎是一种严重的致盲性眼病。Toll 样受体（TLR）是曲霉菌（AF）在角膜中引发固有免疫的关键介质，但固有免疫与适应性免疫之间的信使仍不清楚。胸腺基质淋巴细胞生成素（TSLP）是适应性免疫的关键因素。在这里，我们研究了 AF 刺激角膜上皮和基质细胞时 TSLP 的表达及其与 TLR 的关系。我们用 TLR 配体酵母聚糖或脂多糖（LPS）、人重组 TSLP 或 AF 菌丝刺激角膜细胞，持续不同时间，同时或不预先抑制 TLR2、TLR4 或 TSLP。通过酶联免疫吸附分析、定量聚合酶链反应或 Western blot 测量 TLR2、TLR4、TSLP、IL-8 和 TNF-α的释放和表达。酵母聚糖或 LPS 刺激角膜细胞可诱导 TSLP 表达上调。增强的 TSLP 表达与 AF 处理人角膜细胞有关；TLR2 或 TLR4 抑制可降低 AF 诱导的 TSLP 水平。人重组 TSLP 增强 TLR2 和 TLR4 的表达；TSLP 的 RNA 干扰可减弱 AF 菌丝刺激的 TLR、IL-8 和 TNF-α表达。这些发现表明，TSLP 参与了由 AF 触发的角膜细胞免疫反应，这与 TLR 功能密切相关，TLR 介导的固有免疫可通过 TSLP 增强。因此，固有免疫可能通过激活 TSLP 将炎症信号传递给适应性免疫；反过来，适应性免疫可能通过 TSLP 对固有免疫产生一定的调节作用。也就是说，TSLP 可以与 AF 刺激的人角膜细胞中 TLR2 和 TLR4 介导的固有免疫相互作用，因此可能在 AF 角膜炎的固有和适应性免疫反应之间充当信使。
