Mycobacterium avium uses apoptotic macrophages as tools for spreading

Background: 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. Methods: Electron, time-lapse video, fluorescence microscopy. Apoptosis was determined by ELISA and TUNEL assays. Autophagy was seen by migration of LC3-1. Results: 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. Conclusion: MAC spreading from cell-to-cell is triggered by the macrophage's attempt to kill the bacterium, undergoing apoptosis. (C) 2010 Elsevier Ltd. All rights reserved.