Cited by 255Tuberculosis Research and EpidemiologyMitochondrial Function and PathologyCell death mechanisms and regulation

A Mechanism of Virulence: Virulent Mycobacterium tuberculosis Strain H37Rv, but Not Attenuated H37Ra, Causes Significant Mitochondrial Inner Membrane Disruption in Macrophages Leading to Necrosis

Chen, Minjian, Gan, Huixian, Remold, Heinz G·2006·The Journal of Immunology

Abstract

Infection of human monocyte-derived macrophages with Mycobacterium tuberculosis at low multiplicities of infection leads 48–72 h after the infection to cell death with the characteristics of apoptosis or necrosis. Predominant induction of one or the other cell death modality depends on differences in mitochondrial membrane perturbation induced by attenuated and virulent strains. Infection of macrophages with the attenuated H37Ra or the virulent H37Rv causes mitochondrial outer membrane permeabilization characterized by cytochrome c release from the mitochondrial intermembrane space and apoptosis. Mitochondrial outer membrane permeabilization is transient, peaks 6 h after infection, and requires Ca2+ flux and B cell chronic lymphocytic leukemia/lymphoma 2-associated protein X translocation into mitochondria. In contrast, only the virulent H37Rv induces significant mitochondrial transmembrane potential (Δψm) loss caused by mitochondrial permeability transition. Dissipation of Δψm also peaks at 6 h after infection, is transient, is inhibited by the classical mitochondrial permeability transition inhibitor cyclosporine A, has a requirement for mitochondrial Ca2+ loading, and is independent of B cell chronic lymphocytic leukemia/lymphoma translocation into the mitochondria. Transient dissipation of Δψm 6 h after infection is essential for the induction of macrophage necrosis by Mtb, a mechanism that allows further dissemination of the pathogen and development of the disease.

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Crossref · 10.4049/jimmunol.176.6.3707

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  • Certain virulent M. tuberculosis strains trigger necrosis by inner mitochondrial membrane rupture.

    “Certain virulent M. tuberculosis strains trigger necrosis by inner mitochondrial membrane rupture (124–127).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [124]

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Authors
Chen, M., Gan, H., & Remold, H. G.
Affiliations
Brigham and Women's Hospital (US)
Venue
The Journal of Immunology
Published
2006-03
Volume
176
Issue
6
Pages
3707-3716
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1909986873
Cited by
255
References
48
Citations by year
2026: 7 · 2025: 9 · 2024: 12 · 2023: 9 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 14 · 2018: 14 · 2017: 18 · 2016: 13 · 2015: 21 · 2014: 14 · 2013: 17 · 2012: 15
FWCI
6.37
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL64884, R01HL064884)
  • National Institute of Allergy and Infectious Diseases (AI50216)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv, H37Ra, virulence mechanisms, macrophage necrosis, mitochondrial permeability transition, mitochondrial membrane potential, cytochrome c release, Bax translocation, calcium flux, cyclosporine, apoptosis, monocyte-derived macrophages
MeSH terms
Calcium, Cations, Divalent, Cell Membrane Permeability, Cells, Cultured, Humans, Macrophages, Microscopy, Electron, Mitochondria, Mycobacterium tuberculosis, Necrosis, Virulence, Leukemia, Lymphocytic, Chronic, B-Cell, Cytochromes c, bcl-2-Associated X Protein, Mitochondrial Membranes

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