Division of Veterinary Pathology, Indian Veterinary Research Institute, Izatnagar 243122, India.
Vet Microbiol. 2013 Aug 30;165(3-4):392-401. doi: 10.1016/j.vetmic.2013.03.030. Epub 2013 Apr 10.
The interaction between Mycobacterium avium subsp. paratuberculosis (Map) and macrophages is a complex process to maximize the chances of their respective survival. Previous studies have shown that Map induces cell death in macrophages, but the mechanism is not known. In the present study, we investigated the mechanism by which Map induces cell death in bovine macrophages using the fluorescent and electron microscopic techniques. The macrophages infected with an equal number of Map (i.e., multiplicity of infection, MOI=1) showed no changes of cell death, but those macrophages infected at MOI=10 showed the morphological changes consistent with apoptosis. Strikingly, the macrophages infected by Map at MOI=50 showed the changes of apoptosis and necrosis. The Map-induced apoptosis was a caspase-dependent mechanism at MOI=10 while it was caspase- and nitric oxide-independent at MOI=50. The results of the present study suggest that the mitochondrial damage following Map infection initiates the cell death processes in macrophages.
分支杆菌 avium subsp. 副结核（Map）与巨噬细胞之间的相互作用是一个复杂的过程，以最大限度地提高它们各自生存的机会。先前的研究表明，Map 诱导巨噬细胞死亡，但机制尚不清楚。在本研究中，我们使用荧光和电子显微镜技术研究了 Map 诱导牛巨噬细胞死亡的机制。感染等量 Map 的巨噬细胞（即感染复数，MOI=1）没有发生细胞死亡变化，但感染 MOI=10 的巨噬细胞显示出与细胞凋亡一致的形态变化。引人注目的是，感染 MOI=50 的巨噬细胞表现出凋亡和坏死的变化。Map 在 MOI=10 诱导的细胞凋亡是 caspase 依赖性机制，而在 MOI=50 时则与 caspase 和一氧化氮无关。本研究结果表明，Map 感染后线粒体损伤启动了巨噬细胞的细胞死亡过程。
