Mycobacterium tuberculosis replicates within necrotic human macrophages

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....

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Bibliographic Details
Published in:The Journal of cell biology 2017-03, Vol.216 (3), p.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: Article
Language:English
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
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201603040