Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Department of Ophthalmology, University of Washington, Seattle, WA, USA.
Microb Pathog. 2024 Apr;189:106606. doi: 10.1016/j.micpath.2024.106606. Epub 2024 Mar 2.
Fungal keratitis (FK) is a highly blinding infectious corneal disease caused by pathogenic fungi. Candida albicans (C. albicans) is one of the main pathogens of fungal keratitis. Extracellular vesicles (EVs), lipid bilayer compartments released by almost all living cells, including fungi, have garnered attention for their role in pathogenic microbial infection and host immune responses in recent years. Studies have reported that pretreating the host with fungal EVs can reduce the inflammatory response of the host when attacked by fungi and reduce the lethality of fungal infection. However, there are no studies that have evaluated whether C. albicans EVs can modulate the inflammatory response associated with C. albicans keratitis. Our study revealed that C. albicans EVs could activate the polymorphonuclear cells (PMNs) and promote their secretion of proinflammatory cytokines and nitric oxide (NO), enhance their phagocytic and fungicidal abilities against C. albicans. C. albicans EVs also induced a proinflammatory response in RAW264.7 cells, which was characterized by increased production of inflammatory cytokines and elevated expression of the chemokine CCL2. Similarly, stimulation of C. albicans EVs to RAW264.7 cells also enhanced the phagocytosis and killing ability of cells against C. albicans. Besides, in our in vivo experiments, after receiving subconjunctival injection of C. albicans EVs, C57BL/6 mice were infected with C. albicans. The results demonstrated that pre-exposure to C. albicans EVs could effectively diminish the severity of keratitis, reduce fungal load and improve prognosis. Overall, we conclude that C. albicans EVs can modulate the function of immune cells and play a protective role in C. albicans keratitis.
真菌性角膜炎（FK）是一种由致病性真菌引起的高度致盲性感染性角膜疾病。白色念珠菌（C. albicans）是真菌性角膜炎的主要病原体之一。近年来，细胞外囊泡（EVs）作为几乎所有活细胞（包括真菌）释放的双层脂膜囊泡，因其在病原微生物感染和宿主免疫反应中的作用而受到关注。研究报道，宿主预先用真菌 EVs 处理，可在真菌攻击时减轻宿主的炎症反应，降低真菌感染的致死率。然而，目前尚无研究评估 C. albicans EVs 是否可以调节与 C. albicans 角膜炎相关的炎症反应。我们的研究表明，C. albicans EVs 可以激活多形核细胞（PMNs），促进其分泌促炎细胞因子和一氧化氮（NO），增强其对 C. albicans 的吞噬和杀菌能力。C. albicans EVs 还可诱导 RAW264.7 细胞发生促炎反应，其特征为促炎细胞因子产生增加，趋化因子 CCL2 表达上调。同样，C. albicans EVs 刺激 RAW264.7 细胞也增强了细胞对 C. albicans 的吞噬和杀伤能力。此外，在我们的体内实验中，C57BL/6 小鼠接受 C. albicans EVs 结膜下注射后感染 C. albicans。结果表明，预先暴露于 C. albicans EVs 可有效减轻角膜炎的严重程度，减少真菌负荷并改善预后。总之，我们得出结论，C. albicans EVs 可以调节免疫细胞的功能，并在 C. albicans 角膜炎中发挥保护作用。
