Dying to Live: How the Death Modality of the Infected Macrophage Affects Immunity to Tuberculosis

  • Maziar Divangahi
  • Samuel M. Behar
  • Heinz Remold
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 783)


Virulent Mycobacterium tuberculosis (Mtb) inhibits apoptosis and triggers necrosis of host macrophages to evade innate delay in the initiation of adaptive immunity. Necrosis is a mechanism used by bacteria to exit macrophage, evade the host defenses, and disseminate while apoptosis is associated with diminished pathogen viability. We have recently demonstrated that eicosanoids regulate cell death program of either human or murine macrophages infected with Mtb. We have defined prostaglandin E2 (PGE2) as a pro-apoptotic host lipid mediator which protects against necrosis. In contrast, lipoxin A4 (LXA4) is a pro-necrotic lipid mediator which suppresses PGE2 synthesis, resulting in mitochondrial damage and inhibition of plasma membrane repair mechanisms; this ultimately leads to the induction of necrosis. Thus, the balance between PGE2 and LXA4 determines whether Mtb-infected macrophages undergo apoptosis or necrosis and this balance determines the outcome of infection.


Mycobacterium tuberculosis (MtbMacrophages Necrosis Apoptosis Extrinsic pathway Intrinsic pathway Mitochondrial outer membrane permeabilization (MOMP) Mitochondrial permeability transition (MPT) Cell death program B-cell lymphoma 2 (Bcl-2) BH3 interacting domain (BID) Bcl-2 associated X Protein (BAX) Bcl-2 homologous antagonist killer (BAK) FLICE-inhibitory protein (FLIPS) Lipoxins (LX) Prostaglandins (PG) Eicosanoids Plasma membrane microdisruptions Mycobacterial antigens BCG vaccine T cell response 



M.D. is supported by the Canadian Institute of Health Research-New Investigator Award. Work in his laboratory is supported by the Canadian Institute of Health Research (CIHR) and The Natural Sciences and Engineering Research Council of Canada (NSERC).


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Meakins-Christie Laboratories, Department of Microbiology and Immunology, Department of MedicineMcGill University Health CentreMontrealCanada
  2. 2.Division of Rheumatology, Immunology, and Allergy, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonCanada

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