Gopalakrishnan Archana, Dietzold Jillian, Salgame Padmini
Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, NJ, USA; Rutgers-Graduate School of Biomedical Sciences, Newark, NJ, USA.
Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, NJ, USA.
Cell Immunol. 2016 Apr;302:11-18. doi: 10.1016/j.cellimm.2015.12.009. Epub 2015 Dec 30.
Accumulating evidence indicates that inflammatory signals required for maximizing effector T cell generation have opposing effects on the development of memory T cell precursors. Toll-like receptor (TLR)2, and TLR9 significantly contribute to the inflammatory milieu and therefore in this study we examined whether the absence of TLR9 alone or the combined absence of TLR2 and TLR9 would affect vaccine-mediated immunity to Mtb. We found that TLR9KO and TLR2/9DKO mice vaccinated with a live Mtb auxotroph, akin to vaccinated WT mice, exhibited early control of Mtb growth in the lungs compared to their naïve counterparts. The granulomatous response, IFNγ production and cellular recruitment to the lungs were also similar in all the vaccinated groups of mice. These findings indicate that there is minimal contribution from TLR2 and TLR9 in generating memory immunity to Mtb with live vaccines. Defining the innate milieu that can drive maximal memory T cell generation with a tuberculosis vaccine needs further inquiry.
越来越多的证据表明，使效应T细胞生成最大化所需的炎症信号对记忆T细胞前体的发育具有相反的作用。Toll样受体（TLR）2和TLR9对炎症环境有显著贡献，因此在本研究中，我们研究了单独缺失TLR9或同时缺失TLR2和TLR9是否会影响疫苗介导的针对结核分枝杆菌（Mtb）的免疫。我们发现，用活的结核分枝杆菌营养缺陷型疫苗接种的TLR9基因敲除（TLR9KO）小鼠和TLR2/9双基因敲除（TLR2/9DKO）小鼠，与接种疫苗的野生型（WT）小鼠类似，与未接种的同窝小鼠相比，其肺部结核分枝杆菌生长得到早期控制。在所有接种疫苗的小鼠组中，肉芽肿反应、干扰素γ（IFNγ）产生以及细胞向肺部的募集也相似。这些发现表明，TLR2和TLR9在通过活疫苗产生针对结核分枝杆菌的记忆免疫方面贡献极小。确定能够通过结核疫苗驱动最大程度记忆T细胞生成的先天环境需要进一步探究。
