Department of Microbiology, Immunology, and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 04023-062, Brazil.
Sci Rep. 2020 Nov 10;10(1):19483. doi: 10.1038/s41598-020-76557-6.
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and may be caused by the species Paracoccidioides brasiliensis. In the lungs, this fungus interacts with epithelial cells, activating host cell signalling pathways, resulting in the production of inflammatory mediators. This event may be initiated through the activation of Pattern-Recognition Receptors such as Toll-like Receptors (TLRs). By interacting with cell wall components, TLR2 is frequently related to fungal infections. In this work, we show that, after 24 h post-infection with P. brasiliensis, A549 lung epithelial cells presented higher TLR2 levels, which is important for IL-8 secretion. Besides, integrins may also participate in pathogen recognition by host cells. We verified that P. brasiliensis increased α3 integrin levels in A549 cells after 5 h of infection and promoted interaction between this receptor and TLR2. However, after 24 h, surprisingly, we verified a decrease of α3 integrin levels, which was dependent on direct contact between fungi and epithelial cells. Likewise, we observed that TLR2 is important to downmodulate α3 integrin levels after 24 h of infection. Thus, P. brasiliensis can modulate the host inflammatory response by exploiting host cell receptors and cell signalling pathways.
球孢子菌病（PCM）是拉丁美洲最常见的系统性真菌病，可能由巴西球孢子菌引起。在肺部，这种真菌与上皮细胞相互作用，激活宿主细胞信号通路，导致炎症介质的产生。这一事件可能是通过激活模式识别受体（如 Toll 样受体（TLR））而引发的。TLR2 通过与细胞壁成分相互作用，常与真菌感染有关。在这项工作中，我们表明，巴西球孢子菌感染 A549 肺上皮细胞 24 小时后，TLR2 水平升高，这对于 IL-8 的分泌很重要。此外，整合素也可能通过宿主细胞参与病原体识别。我们验证了巴西球孢子菌在感染后 5 小时增加了 A549 细胞中 α3 整合素的水平，并促进了该受体与 TLR2 之间的相互作用。然而，令人惊讶的是，在 24 小时后，我们发现 α3 整合素的水平下降，这取决于真菌和上皮细胞之间的直接接触。同样，我们观察到 TLR2 对于在感染后 24 小时下调 α3 整合素水平很重要。因此，巴西球孢子菌可以通过利用宿主细胞受体和细胞信号通路来调节宿主的炎症反应。
