Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis
Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis
复制标题
DOI：
10.1172/jci31947
复制
发表时间：
2007-08-01
影响因子：
15.9
通讯作者：
Porcelli, Steven A.
中科院分区：
文献类型：
--
作者：
Hinchey, Joseph;Lee, Sunhee;Porcelli, Steven A.
抑制感染宿主细胞的凋亡是致病分枝杆菌的一个众所周知但知之甚少的功能。我们发现，结核分枝杆菌secA2基因的失活，通过减少分枝杆菌超氧化物歧化酶的分泌，增强了感染的巨噬细胞的凋亡。缺失secA2可显著增强体内抗原特异性CD8(+)T细胞的免疫应答，与标准牛分枝杆菌卡介苗相比，secA2突变体免疫小鼠和豚鼠可显著增强对结核分枝杆菌攻击的抵抗力。我们的结果确定了结核分枝杆菌关键免疫逃避策略的机制，并提供了一种我们认为是改进分枝杆菌疫苗的新方法。
The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. Deletion of secA2 markedly increased priming of antigen-specific CD8(+) T cells in vivo, and vaccination of mice and guinea pigs with a secA2 mutant significantly increased resistance to M. tuberculosis challenge compared with standard M. bovis bacille Calmette-Guerin vaccination. Our results define a mechanism for a key immune evasion strategy of M. tuberculosis and provide what we believe to be a novel approach for improving mycobacterial vaccines.