Mycobacterium tuberculosis replicates within necrotic human macrophages

• Published in: The Journal of cell biology Vol. 216; no. 3; pp. 583 - 594
• Main Authors: Lerner, Thomas R, Borel, Sophie, Greenwood, Daniel J, Repnik, Urska, Russell, Matthew R G, Herbst, Susanne, Jones, Martin L, Collinson, Lucy M, Griffiths, Gareth, Gutierrez, Maximiliano G
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06.03.2017; The Rockefeller University Press
• Subjects: Apoptosis; Bacteria; Cell Death - genetics; Cell Differentiation - genetics; Cells; Cells, Cultured; DNA Replication - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Humans; Interferon-gamma - genetics; Leukocytes, Mononuclear - microbiology; Macrophage Colony-Stimulating Factor - genetics; Macrophages - microbiology; Membranes; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Necrosis - genetics; Single-Cell Analysis
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201603040

modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. In this study, we investigate the impact of plasma membrane (PM) integrity on bacterial replication in different functional populations of human primary macrophages. We discovered that IFN-γ enhanced bacterial replication in macrophage colony-stimulating factor-differentiated macrophages more than in granulocyte-macrophage colony-stimulating factor-differentiated macrophages. We show that permissiveness in the different populations of macrophages to bacterial growth is the result of a differential ability to preserve PM integrity. By combining live-cell imaging, correlative light electron microscopy, and single-cell analysis, we found that after infection, a population of macrophages became necrotic, providing a niche for replication before escaping into the extracellular milieu. Thus, in addition to bacterial dissemination, necrotic cells provide first a niche for bacterial replication. Our results are relevant to understanding the environment of replication in the host.