Faculty of Medicine, University of Oslo, Norway.
Med Mycol. 2011 May;49(4):375-9. doi: 10.3109/13693786.2010.531772. Epub 2010 Nov 10.
Toll-like receptors (TLRs) are involved in the host defense against Aspergillus fumigatus infections, and some TLRs may even be exploited by the mould to escape immune mechanisms. We have previously shown that conidia from A. fumigatus increase expression of TLR5 in human monocytes. When further investigating a possible role of TLR5 in A. fumigatus infections, we observed a decrease in conidial viability after culturing with TLR5-knockdown THP-1 monocytes. Secondly, our experiments showed an increase in conidial viability when THP-1 monocytes, together with flagellin, are cultured with conidia. Thirdly, we found that treatment of THP-1 monocytes with a monoclonal antibody against TLR5 resulted in increased conidial viability after culturing. Experiments with a HEK-293 cell line only expressing TLR5 did not indicate that conidia directly interact with TLR5. Further studies of the intracellular molecular mechanisms activated concomitant with activation of TLR5 that have an enhancing effect on the viability of conidia may shed new light on the defense against conidia in monocytic cells, and possibly also on the function of the TLR5 system.
Toll 样受体(TLRs)参与宿主对抗烟曲霉感染的防御,一些 TLR 甚至可能被霉菌利用来逃避免疫机制。我们之前已经表明,烟曲霉的分生孢子会增加人单核细胞中 TLR5 的表达。当进一步研究 TLR5 在烟曲霉感染中的可能作用时,我们观察到与 TLR5 敲低的 THP-1 单核细胞培养后,分生孢子的活力下降。其次,我们的实验表明,当 THP-1 单核细胞与鞭毛蛋白一起培养时,分生孢子的活力增加。第三,我们发现用针对 TLR5 的单克隆抗体处理 THP-1 单核细胞后,培养后的分生孢子活力增加。仅表达 TLR5 的 HEK-293 细胞系的实验表明,分生孢子不会直接与 TLR5 相互作用。进一步研究激活 TLR5 时伴随的细胞内分子机制,这些机制对分生孢子的活力有增强作用,可能为单核细胞中对抗分生孢子的防御机制,以及可能为 TLR5 系统的功能提供新的认识。