Department of Microbiology, Immunology, and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862-Ed. Antônio C. M. Paiva-6 andar, São Paulo, SP, 04023-062, Brazil.
Med Microbiol Immunol. 2020 Feb;209(1):59-67. doi: 10.1007/s00430-019-00639-0. Epub 2019 Oct 31.
Fungi that belong to the genus Paracoccidioides are the etiologic agents of paracoccidioidomycosis, a human systemic mycosis, which occurs in Latin America. Epithelial cell is one of the first cells that interact with these fungi and responds by secreting inflammatory mediators such as cytokines. In the present study, we demonstrate that yeasts of different isolates of Paracoccidioides brasiliensis (Pb18 and Pb03) and Paracoccidioides lutzii (Pb01) distinctly promoted interleukin (IL)-8 secretion by the lung epithelial cell line A549. Depending on the isolate, this cytokine release may rely on the epithelial cell interaction with fungal secreted components or direct contact with the pathogen. In addition, adhesion of yeasts to the pulmonary epithelial cells was also different among Paracoccidioides isolates, and the highest percentage of A549 cells with adhered fungi was observed with P. lutzii. All Paracoccidioides isolates induced an expression increase of α3 and α5 integrins in A549 cells and, using small interfering RNA, we observed that the integrin silencing promoted a reduction of P. lutzii adhesion, which suggests the involvement of integrins in this event. Together, these results indicate that host epithelial cell response may depend on the isolate of Paracoccidioides.
属于巴西副球孢子菌属的真菌是副球孢子菌病的病原体,这是一种人类系统性真菌病,发生在拉丁美洲。上皮细胞是与这些真菌最早相互作用的细胞之一,并通过分泌细胞因子等炎症介质来响应。在本研究中,我们证明了不同巴西副球孢子菌(Pb18 和 Pb03)和秘鲁副球孢子菌(Pb01)分离株的酵母明显促进了肺上皮细胞系 A549 分泌白细胞介素(IL)-8。根据分离株的不同,这种细胞因子的释放可能依赖于上皮细胞与真菌分泌成分的相互作用或与病原体的直接接触。此外,酵母对肺上皮细胞的黏附在不同的副球孢子菌分离株之间也存在差异,并且在用秘鲁副球孢子菌黏附的 A549 细胞中观察到最高的百分比。所有副球孢子菌分离株均诱导 A549 细胞中α3 和α5 整合素的表达增加,并且使用小干扰 RNA,我们观察到整合素沉默促进了秘鲁副球孢子菌的黏附减少,这表明整合素参与了这一事件。总之,这些结果表明宿主上皮细胞的反应可能取决于副球孢子菌的分离株。