Mycobacterium bovis Bacillus Calmette Guerin infection prevents apoptosis of resting human monocytes
Mycobacterium bovis Bacillus Calmette Guerin infection prevents apoptosis of resting human monocytes
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DOI：
10.1002/eji.1830270945
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发表时间：
1997-09-01
影响因子：
5.4
通讯作者：
Locht, C
中科院分区：
文献类型：
--
作者：
Kremer, L;Estaquier, J;Locht, C
细胞凋亡在多细胞生物的发育和稳态中起着重要作用。一些传染性病原体干扰这种程序性细胞死亡以获得自身利益。在这里，我们表明，用牛分枝杆菌卡介苗（BCG）感染静息的人单核细胞，通过阻止单核细胞凋亡来增加单核细胞的活力。热灭活的BCG也防止细胞凋亡，表明BCG的复制不是防止细胞死亡所必需的。BCG感染的单核细胞的分析显示A1 mRNA的上调，而bcl-2 mRNA没有上调，有趣的是，BCG预感染使细胞对白细胞介素（IL）-10诱导的凋亡具有抗性，这可能是分枝杆菌用于调节免疫应答的机制之一。BCG感染还伴随着单核细胞分泌IL-10的能力的损害和分泌肿瘤坏死因子-α的能力的诱导，这两种细胞因子已知分别诱导和预防人单核细胞凋亡。由于已经报道细胞凋亡参与细胞内分枝杆菌的杀伤，因此防止细胞凋亡可能代表分枝杆菌在感染宿主中存活的策略。
Apoptosis plays an essential role in the development and homeostasis of multicellular organisms. Some infectious agents interfere with this programmed cell death to their own benefit. Here, we show that infection of resting human monocytes with Mycobacterium bovis Bacillus Calmette Guerin (BCG) increases monocyte viability by preventing them from undergoing apoptosis. Heat-killed BCG also prevented apoptosis, indicating that replication of BCG is not required to prevent cell death. Analysis of BCG-infected monocytes revealed an up-regulation of the A1 mRNA, whereas the bcl-2 mRNA was not up-regulated, interestingly, preinfection with BCG renders the cells resistant to interleukin (IL)-10-induced apoptosis which may be one of the mechanisms mycobacteria use to modulate immune responses. BCG infection was also accompanied by an impairment of the capacity of monocytes to secrete IL-10 and by an induction of the capacity to secrete tumor necrosis factor-alpha, two cytokines known to induce and prevent human monocyte apoptosis, respectively. Since it has been reported that apoptosis is involved in killing of intracellular mycobacteria, the prevention of apoptosis may represent a strategy for mycobacterial survival in the infected host.