Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis
- PMID: 21307848
- PMCID: PMC3155700
- DOI: 10.1038/mi.2011.3
Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis
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.
Conflict of interest statement
The authors declared no conflict of interest.
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Comment in
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The impact of mucosal infections on acquisition and progression of tuberculosis.Mucosal Immunol. 2011 May;4(3):246-51. doi: 10.1038/mi.2011.11. Epub 2011 Mar 16. Mucosal Immunol. 2011. PMID: 21412228 Free PMC article. Review.
References
-
- Schlesinger LS, Kaufman TM, Iyer S, Hull SR, Marchiando LK. Differences in mannose receptor-mediated uptake of lipoarabinomannan from virulent and attenuated strains of Mycobacterium tuberculosis by human macrophages. J Immunol. 1996;157:4568–4575. - PubMed
-
- Sturgill-Koszycki S, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase [see comments] [published erratum appears in Science 1994 11 March;263(5152):1359] Science. 1994;263:678–681. - PubMed
-
- Chen M, Gan H, Remold HG. A mechanism of virulence: virulent Mtb tuberculosis strain H37Rv but not attenuated H37Ra causes significant mitochondrial inner membrane disruption in macrophages leading to necrosis. J Immunol. 2006;176:3707–3716. - PubMed
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