title: Mycobacterium tuberculosisreplicates within necrotic human macrophages.
abstract: Mycobacterium tuberculosismodulation 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 forM. tuberculosisreplication 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 ofM. tuberculosisreplication in the host.
authors.affiliation: Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Lerner
authors.affiliation: Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Sophie
authors.identifier: 0000-0001-8643-224X
authors.initials: S
authors.lastname: Borel
authors.affiliation: Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Daniel J
authors.identifier: 0000-0002-7407-506X
authors.initials: DJ
authors.lastname: Greenwood
authors.affiliation: Department of Biosciences, University of Oslo, 0371 Oslo, Norway.
authors.forename: Urska
authors.initials: U
authors.lastname: Repnik
authors.affiliation: Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Matthew R G
authors.identifier: 0000-0003-4608-7669
authors.initials: MR
authors.lastname: Russell
authors.affiliation: Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Susanne
authors.initials: S
authors.lastname: Herbst
authors.affiliation: Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Martin L
authors.identifier: 0000-0003-0994-5652
authors.initials: ML
authors.lastname: Jones
authors.affiliation: Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, England, UK.
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Collinson
authors.affiliation: Department of Biosciences, University of Oslo, 0371 Oslo, Norway.
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.affiliation: Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, England, UK max.g@crick.ac.uk.
authors.forename: Maximiliano G
authors.identifier: 0000-0003-3199-0337
authors.initials: MG
authors.lastname: Gutierrez
mesh_terms: D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004261:DNA Replication / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D009336:Necrosis / Q000235:genetics*; D059010:Single-Cell Analysis
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor