Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis

S. M. Behar, C. J. Martin, M. G. Booty, T. Nishimura, X. Zhao, H. X. Gan, M. Divangahi, H. G. Remold

Research output: Contribution to journalReview article

203 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)279-287
Number of pages9
JournalMucosal Immunology
Volume4
Issue number3
DOIs
Publication statusPublished - 2011 May

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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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). Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunology, 4(3), 279-287. https://doi.org/10.1038/mi.2011.3