Department of ophthalmology, The First Affiliated Hospital of USTC, Division of life sciences and medicine, University of Science and Technology of China, No. 17, Lujiang Road, Hefei, 230001, Anhui, China.
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Kirrberger Strasse 100 Geb. 22, 66424, Homburg, Saarland, Germany.
Inflammation. 2021 Apr;44(2):682-692. doi: 10.1007/s10753-020-01367-x. Epub 2020 Oct 28.
Fungal keratitis (FK) is a keratopathy caused by pathogenic fungal infection. The aim of this work is to explore the role of thymic stromal lymphopoietin (TSLP) in FK. Human corneal epithelial cells (HCECs) were treated with Aspergillus fumigatus hyphae, and we found that TSLP was highly expressed and secreted in the hyphae-treated HCECs. Hyphae-treated HCECs or TSLP treatment enhanced the expression of caspase-1 P20, GSDMD-N (p30), IL-1β, and IL-18 in the human THP-1 macrophages. The influence conferred by hyphae-treated HCECs or TSLP treatment was rescued by TSLP neutralizing antibody or VX-765 (caspase-1 inhibitor) treatment. Moreover, TSLP treatment promoted the expression of NLRP3, ASC, caspase-1 P20, GSDMD-N (p30), IL-1β, and IL-18 in the THP-1 macrophages, which was abolished by NLRP3 knockdown. Furthermore, TSLPR silencing suppressed the expression of NLRP3, ASC, caspase-1 P20, GSDMD-N (p30), IL-1β, and IL-18 in the TSLP-treated THP-1 macrophages. In conclusion, our article confirms that Aspergillus fumigatus-stimulated HCECs induce pyroptosis of THP-1 macrophages by secreting TSLP. TSLP/TSLPR induces caspase-1-dependent pyroptosis through activation of NLRP3 inflammasome. Thus, our work suggests that TSLP may be a potential target for FK treatment.
真菌性角膜炎（FK）是一种由致病真菌感染引起的角膜病变。本工作旨在探讨胸腺基质淋巴细胞生成素（TSLP）在 FK 中的作用。我们用烟曲霉菌丝体处理人角膜上皮细胞（HCEC），发现 TSLP 在菌丝体处理的 HCEC 中高度表达和分泌。菌丝体处理的 HCEC 或 TSLP 处理增强了人 THP-1 巨噬细胞中 caspase-1 P20、GSDMD-N（p30）、IL-1β 和 IL-18 的表达。TSLP 中和抗体或 VX-765（caspase-1 抑制剂）处理可挽救菌丝体处理的 HCEC 或 TSLP 处理的影响。此外，TSLP 处理促进了 THP-1 巨噬细胞中 NLRP3、ASC、caspase-1 P20、GSDMD-N（p30）、IL-1β 和 IL-18 的表达，而 NLRP3 敲低则消除了这种表达。此外，TSLPR 沉默抑制了 TSLP 处理的 THP-1 巨噬细胞中 NLRP3、ASC、caspase-1 P20、GSDMD-N（p30）、IL-1β 和 IL-18 的表达。总之，我们的文章证实，烟曲霉刺激的 HCEC 通过分泌 TSLP 诱导 THP-1 巨噬细胞发生细胞焦亡。TSLP/TSLPR 通过激活 NLRP3 炎性体诱导 caspase-1 依赖性细胞焦亡。因此，我们的工作表明 TSLP 可能是 FK 治疗的潜在靶点。
