Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil.
Departamento de Imunologia, do Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Front Cell Infect Microbiol. 2019 Jan 10;8:426. doi: 10.3389/fcimb.2018.00426. eCollection 2018.
Toll-like receptors (TLRs) comprise the best-characterized pattern-recognition receptor (PRR) family able to activate distinct immune responses depending on the receptor/adaptor set assembled. TLRs, such as TLR2, TLR4 and TLR9, and their signaling were shown to be important in infections. However, the role of the endosomal TLR3 in experimental paracoccidioidomycosys remains obscure. assays, macrophages of the bone marrow of WT or TLR3 mice were differentiated for evaluation of their microbicidal activity. , WT or TLR3 mice were infected intratracheally with yeasts for investigation of the lung response type induced. The cytotoxic activity of CD8 T cells was assessed by cytotoxicity assay. To confirm the importance of CD8 T cells in the control of infection in the absence of tlr3, a depletion assay of these cells was performed. Here, we show for the first time that TLR3 modulate the infection against by dampening pro-inflammatory response, NO production, IFNCD8T, and IL-17CD8T cell activation and cytotoxic function, associated with granzyme B and perforin down regulation. As conclusion, we suggest that TLR3 could be used as an escape mechanism of the fungus in an experimental paracoccidioidomycosis.
Toll 样受体 (TLRs) 构成了最佳特征化的模式识别受体 (PRR) 家族，能够根据组装的受体/衔接子集激活不同的免疫反应。TLRs，如 TLR2、TLR4 和 TLR9，及其信号转导被证明在 感染中很重要。然而，内体 TLR3 在实验性副球孢子菌病中的作用仍然不清楚。 实验中，用 WT 或 TLR3 小鼠的骨髓巨噬细胞进行分化，以评估其杀菌活性。 然后，WT 或 TLR3 小鼠通过气管内感染酵母来研究诱导的肺部反应类型。通过细胞毒性测定评估 CD8 T 细胞的细胞毒性活性。为了确认在没有 tlr3 的情况下控制感染中 CD8 T 细胞的重要性，进行了这些细胞的耗竭测定。在这里，我们首次表明 TLR3 通过抑制促炎反应、NO 产生、IFNCD8T 和 IL-17CD8T 细胞激活和细胞毒性功能来调节对 的感染，与颗粒酶 B 和穿孔素下调相关。因此，我们认为 TLR3 可作为真菌在实验性副球孢子菌病中的逃逸机制。
