Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells.

ABSTRACT: A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in liv

SUBMITTER: Mahamed D 

PROVIDER: S-EPMC5319838 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature