The State Key Lab of Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National TSE Lab, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
Vet Microbiol. 2012 Nov 9;160(1-2):117-25. doi: 10.1016/j.vetmic.2012.05.011. Epub 2012 May 18.
Mycobacterium bovis parasitizes host macrophages and has developed strategies to survive within macrophages. Research on mycobacteria-specific PE_PGRS genes indicates that they code for cell surface proteins that may influence virulence. To further elucidate the molecular pathogenesis of tuberculosis and host response to M. bovis, we explored the mechanisms by which PE_PGRS62 protein increase persistence of mycobacterium within host macrophages. We found that the M. smegmatis strain expressing M. bovis PE_PGRS 62 protein reduced phagolysosome maturation in human macrophages, and significantly decreased the mRNA expression of IL-1β in a dose- and time-dependent. We identified that IFN-γ priming of macrophages immediately prior to infection with PE_PGRS62 expressing M. smegmantis, enhanced the maturation of phagolysosomes and induced IL-1β production both that the protein and mRNA levels and further activated the NF-κB pathway. Overall, we demonstrated that PE_PGRS62 protein altered the immune environment of the host cells, which suggested that the pathogenic PE_PGRS62 protein altering the immune mechanism might be involved in the pathogenesis of mycobacterial disease and hence influenced host cell responses to M. bovis infection.
牛分枝杆菌寄生于宿主巨噬细胞内，并发展出多种生存策略。对分枝杆菌特异性 PE_PGRS 基因的研究表明，它们编码的细胞表面蛋白可能影响毒力。为了进一步阐明结核病的分子发病机制和宿主对牛分枝杆菌的反应，我们探讨了 PE_PGRS62 蛋白增加分枝杆菌在宿主巨噬细胞中持续存在的机制。我们发现，表达牛分枝杆菌 PE_PGRS62 蛋白的耻垢分枝杆菌菌株减少了人巨噬细胞中的吞噬体成熟，并呈剂量和时间依赖性显著降低 IL-1β 的 mRNA 表达。我们确定，在感染表达 PE_PGRS62 的耻垢分枝杆菌之前，用 IFN-γ 对巨噬细胞进行预处理，可增强吞噬体的成熟，并诱导 IL-1β 的产生，蛋白和 mRNA 水平均升高，并进一步激活 NF-κB 通路。总体而言，我们证明了 PE_PGRS62 蛋白改变了宿主细胞的免疫环境，这表明致病性 PE_PGRS62 蛋白改变免疫机制可能参与了分枝杆菌病的发病机制，并因此影响宿主细胞对牛分枝杆菌感染的反应。
