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Cited by 447Tuberculosis Research and EpidemiologyCell death mechanisms and regulationImmune responses and vaccinations

Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis

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Behar, S M, Martin, C J, Booty, M G, Nishimura, T, Zhao, X, Gan, H-X, Divangahi, M, Remold, H G·2011·Mucosal Immunology
DOI 10.1038/mi.2011.3PMC PMC3155700
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Abstract

Two different forms of death are commonly observed when Mycobacterium tuberculosis (Mtb)-infected macrophages die: (i) necrosis, a death modality defined by cell lysis and (ii) apoptosis, a form of death that maintains an intact plasma membrane. Necrosis is a mechanism used by bacteria to exit the macrophage, evade host defenses, and spread. In contrast, apoptosis of infected macrophages is associated with diminished pathogen viability. Apoptosis occurs when tumor necrosis factor activates the extrinsic death domain pathway, leading to caspase-8 activation. In addition, mitochondrial outer membrane permeabilization leading to activation of the intrinsic apoptotic pathway is required. Both pathways lead to caspase-3 activation, which results in apoptosis. We have recently demonstrated that during mycobacterial infection, cell death is regulated by the eicosanoids, prostaglandin E(2) (proapoptotic) and lipoxin (LX)A(4) (pronecrotic). Although PGE(2) protects against necrosis, virulent Mtb induces LXA(4) and inhibits PGE(2) production. Under such conditions, mitochondrial inner membrane damage leads to macrophage necrosis. Thus, virulent Mtb subverts eicosanoid regulation of cell death to foil innate defense mechanisms of the macrophage.

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  • Cytokines are main promoters of apoptosis, particularly TNF.

    “as cytokines are main promoters of apoptosis, particularly TNF [48, 49].”

    From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [48]

    In “Induction of apoptosis through the extrinsic pathway in Mtb-infected macrophages” (page not provided), the paper identifies TNF as the cytokine-dependent signal required for apoptosis in that setting. It also says a lipid-dependent signal is required, so it does not establish the broader claim that cytokines are the main promoters of apoptosis generally. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Behar, S. M., Martin, C. J., Booty, M. G., Nishimura, T., Zhao, X., Gan, H.-X., Divangahi, M., & Remold, H. G.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Remold, H G
ORCID
Venue
Mucosal Immunology
Publisher
Elsevier BV
Published
2011-05
Volume
4
Issue
3
Pages
279-287
ISSN
1933-0219 (ISSN-L)
DOI
10.1038/mi.2011.3
PMC
PMC3155700
OpenAlex
W2147098153
Cited by
447
References
4
Citations by year
2026: 27 · 2025: 26 · 2024: 25 · 2023: 34 · 2022: 36 · 2021: 29 · 2020: 32 · 2019: 28 · 2018: 32 · 2017: 39 · 2016: 32 · 2015: 34 · 2014: 25 · 2013: 23 · 2012: 19
FWCI
2.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Mucosal Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R01AI047171, R01AI072143, R01-AI-47171, R21AI050216, R01AI098637, AI50216, R01AI067731, AI072143, R01AI050216)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
apoptosis, macrophages, Mycobacterium tuberculosis, necrosis, eicosanoids, prostaglandin E2, lipoxin A4, mitochondrial outer membrane permeabilization, caspase-8, caspase-3, bacterial virulence, innate immunity, host-pathogen interaction
MeSH terms
Animals, Gene Expression Regulation, Humans, Mycobacterium tuberculosis, Necrosis, Tuberculosis, Pulmonary, Eicosanoids, Macrophages, Alveolar, Apoptosis, Immunity, Mucosal, Immune Evasion

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