Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques.
Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques.
复制标题
在分枝杆菌感染的恒河猴中，Th1 组织对分枝杆菌糖脂的反应偏向。
DOI：
10.1016/j.bbrc.2013.10.021
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Sugita M
中科院分区：
文献类型：
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作者：
Morita D;Miyamoto A;Hattori Y;Komori T;Nakamura T;lgarashi T;Harashima H;Sugita M
海藻糖6,6'-二霉菌酸酯（TDM）是分枝杆菌细胞壁的主要糖脂，具有显着的辅助功能。为了避免被宿主先天免疫系统检测到，入侵的分枝杆菌利用宿主来源的葡萄糖作为其分枝杆菌转移酶的竞争性底物来下调 TDM 的表达；然而，这种酶促反应会导致葡萄糖单菌酸 (GMM) 的同时生物合成，从而被获得性免疫系统识别。在受感染的人类受试者和猴子的外周血以及小动物（如豚鼠和人类 CD1 转基因小鼠）的次级淋巴器官中检测到 GMM 特异性、CD1 限制性 T 细胞反应。然而，GMM 产生部位的组织如何反应仍有待确定。在这里，我们发现，接种了牛分枝杆菌卡介苗的恒河猴在受 GMM 攻击的皮肤中产生了趋化因子反应，有利于招募 T 辅助 (Th)1 T 细胞。事实上，在注射 GMM 的组织中，干扰素-γ 的表达显着，但 Th2 或 Th17 细胞因子的表达不显着。 GMM 引发的组织反应还与单核细胞/巨噬细胞吸引 CC 趋化因子（例如 CCL2、CCL4 和 CCL8）的表达相关。此外，皮肤对 GMM 的反应涉及颗粒溶素和穿孔素表达上调。鉴于 GMM 主要是由宿主内增殖的病原分枝杆菌产生的，对 GMM 的 Th1 偏向组织反应可能在感染部位有效发挥作用。
Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated withMycobacterium bovisbacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.