Department of Microbiology, and Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, South Korea.
Department of Microbiology, and Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, South Korea.
Cell Immunol. 2018 Jun;328:70-78. doi: 10.1016/j.cellimm.2018.03.012. Epub 2018 Mar 31.
Tuberculosis remains a serious health problem worldwide. Characterization of the dendritic cell (DC)-activating mycobacterial proteins has driven the development of effective TB vaccine candidates besides improving the understanding of immune responses. Some studies have emphasized the essential role of protein Rv2220 from M. tuberculosis in mycobacterial growth. Nonetheless, little is known about cellular immune responses to Rv2220. In this study, our aim was to test whether protein Rv2220 induces maturation and activation of DCs. Rv2220-activated DCs appeared to be in a mature state with elevated expression of relevant surface molecules and proinflammatory cytokines. DC maturation caused by Rv2220 was mediated by MAPK and NF-κB signaling pathways. Specifically, Rv2220-matured DCs induced the expansion of memory CD62LCD44CD4 T cells in the spleen of mycobacteria-infected mice. Our results suggest that Rv2220 regulates host immune responses through maturation of DCs, a finding that points to a new vaccine candidate against tuberculosis.
结核病仍然是一个严重的全球健康问题。分枝杆菌激活树突状细胞(DC)的蛋白特征,除了提高对免疫反应的理解之外,还推动了有效结核病疫苗候选物的发展。一些研究强调了结核分枝杆菌蛋白 Rv2220 在分枝杆菌生长中的重要作用。然而,人们对 Rv2220 的细胞免疫反应知之甚少。在这项研究中,我们的目的是测试蛋白 Rv2220 是否诱导 DC 的成熟和激活。Rv2220 激活的 DC 似乎处于成熟状态,相关表面分子和促炎细胞因子的表达水平升高。Rv2220 引起的 DC 成熟是通过 MAPK 和 NF-κB 信号通路介导的。具体来说,Rv2220 成熟的 DC 诱导感染分枝杆菌的小鼠脾脏中记忆性 CD62L+CD44+CD4 T 细胞的扩增。我们的研究结果表明,Rv2220 通过 DC 的成熟来调节宿主免疫反应,这一发现为结核病的新型疫苗候选物指明了方向。