Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21045-900, Brazil.
Sci Rep. 2021 Jan 14;11(1):1407. doi: 10.1038/s41598-021-80959-5.
Toll-like receptor 9 (TLR9) is crucial to the host immune response against fungi, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, but its importance in Cryptococcus gattii infection is unknown. Our study aimed to understand the role of TLR9 during the course of experimental C. gattii infection in vivo, considering that the cryptococcal DNA interaction with the receptor could contribute to host immunity even in an extremely susceptible model. We inoculated C57BL/6 (WT) and TLR9 knock-out (TLR9) mice intratracheally with 10 C. gattii yeast cells. TLR9 mice had a higher mortality rate compared to WT mice and more yeast cells that had abnormal size, known as titan cells, in the lungs. TLR9 mice also had a greater number of CFUs in the spleen and brain than WT mice, in addition to having lower levels of IFN-γ and IL-17 in the lung. With these markers of aggressive cryptococcosis, we can state that TLR9 mice are more susceptible to C. gattii, probably due to a mechanism associated with the decrease of a Th1 and Th17-type immune response that promotes the formation of titan cells in the lungs. Therefore, our results indicate the participation of TLR9 in murine resistance to C. gattii infection.
Toll 样受体 9（TLR9）对于宿主对真菌（如白色念珠菌、烟曲霉和新生隐球菌）的免疫反应至关重要，但它在新型隐球菌感染中的重要性尚不清楚。我们的研究旨在了解 TLR9 在体内实验性新型隐球菌感染过程中的作用，因为隐球菌 DNA 与受体的相互作用即使在极易感的模型中也有助于宿主免疫。我们通过气管内接种 10 个新型隐球菌酵母细胞，将 C57BL/6（WT）和 TLR9 敲除（TLR9）小鼠感染新型隐球菌。与 WT 小鼠相比，TLR9 小鼠的死亡率更高，肺部的酵母细胞体积异常增大，称为泰坦细胞。与 WT 小鼠相比，TLR9 小鼠的脾和脑中的 CFU 数量更多，此外，肺中的 IFN-γ 和 IL-17 水平更低。有了这些侵袭性隐球菌的标志物，我们可以说 TLR9 小鼠更容易感染新型隐球菌，这可能是由于与 Th1 和 Th17 型免疫反应下降相关的机制，该机制促进了肺部泰坦细胞的形成。因此，我们的结果表明 TLR9 参与了小鼠对新型隐球菌感染的抵抗。
