Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Microb Pathog. 2011 Feb;50(2):132-9. doi: 10.1016/j.micpath.2010.12.004. Epub 2010 Dec 15.
Mycobacterium avium (MAC) lives and replicates in macrophages and causes disseminated disease in immunocompromised individuals. As a host response to control disease, many macrophages become apoptotic a few days after MAC infection. In this study, we hypothesized that MAC can survive autophagic and apoptotic macrophages and spread.
Electron, time-lapse video, fluorescence microscopy. Apoptosis was determined by ELISA and TUNEL assays. Autophagy was seen by migration of LC3-1.
Apoptotic macrophages harbor chiefly viable MAC. MAC escapes both the vacuole and the macrophage once apoptosis is triggered, leaving the bacteria free to infect nearby macrophages in the process of spreading. In addition, some MAC species will have apoptotic bodies and are released in healthy macrophages following apoptotic body ingestion. Because autophagy precedes apoptosis, it was established that heat-killed MAC, and viable MAC induces autophagy in macrophages at similar rates, but MAC still survives.
MAC spreading from cell-to-cell is triggered by the macrophage's attempt to kill the bacterium, undergoing apoptosis.
鸟分枝杆菌(MAC)在巨噬细胞中生存和复制,并在免疫功能低下的个体中引起播散性疾病。作为宿主控制疾病的反应,许多巨噬细胞在 MAC 感染后几天内会发生凋亡。在这项研究中,我们假设 MAC 可以在自噬和凋亡的巨噬细胞中存活并传播。
电子显微镜、延时视频、荧光显微镜。通过 ELISA 和 TUNEL 检测确定细胞凋亡。通过 LC3-1 的迁移来观察自噬。
凋亡的巨噬细胞主要携带活的 MAC。一旦触发凋亡,MAC 就会从吞噬体和巨噬细胞中逃脱,从而使细菌能够在传播过程中自由感染附近的巨噬细胞。此外,一些 MAC 物种将含有凋亡小体,并且在凋亡小体被健康的巨噬细胞吞噬后被释放。由于自噬先于凋亡发生,因此可以确定热灭活的 MAC 和活的 MAC 以相似的速度诱导巨噬细胞中的自噬,但 MAC 仍能存活。
MAC 通过细胞间的传播是由巨噬细胞试图杀死细菌而触发的,这个过程中巨噬细胞会发生凋亡。