ESX-1-induced apoptosis during mycobacterial infection: to be or not to be, that is the question

The major Mycobacterium tuberculosis virulence factor ESAT-6 exported by the ESX-1 secretion system has been described as a pro-apoptotic factor by several independent groups in recent years, sustaining a role for apoptosis in M. tuberculosis pathogenesis. This role has been supported by independent studies in which apoptosis has been shown as a hallmark feature in human and mouse lungs infected with virulent strains. Nevertheless, the role of apoptosis during mycobacterial infection is subject to an intense debate. Several works maintain that apoptosis is more evident with attenuated strains, whereas virulent mycobacteria tend to inhibit this process, suggesting that apoptosis induction may be a host mechanism to control infection. In this review, we summarize the evidences that support the involvement of ESX-1-induced apoptosis in virulence, intending to provide a rational treatise for the role of programmed cell death during M. tuberculosis infection.

[1]  T. Kaisho,et al.  Corrigendum: Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages , 2007, Nature Immunology.

[2]  I. Kawamura,et al.  The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation. , 2014, Pathogens and disease.

[3]  J. Badiola,et al.  ESX‐1‐induced apoptosis is involved in cell‐to‐cell spread of Mycobacterium tuberculosis , 2013, Cellular microbiology.

[4]  B. Gicquel,et al.  Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials. , 2013, Vaccine.

[5]  L. Ramakrishnan,et al.  TNF Dually Mediates Resistance and Susceptibility to Mycobacteria via Mitochondrial Reactive Oxygen Species , 2013, Cell.

[6]  Hwa‐Jung Kim,et al.  Mycobacterium kansasii-induced death of murine macrophages involves endoplasmic reticulum stress responses mediated by reactive oxygen species generation or calpain activation , 2013, Apoptosis.

[7]  B. Robertson,et al.  The Balance of Apoptotic and Necrotic Cell Death in Mycobacterium tuberculosis Infected Macrophages Is Not Dependent on Bacterial Virulence , 2012, PloS one.

[8]  J. Badiola,et al.  Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death , 2012, PloS one.

[9]  S. Fortune,et al.  Efferocytosis is an innate antibacterial mechanism. , 2012, Cell host & microbe.

[10]  E. Coccia,et al.  ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells , 2012, Autophagy.

[11]  P. Peters,et al.  ESX‐1‐mediated translocation to the cytosol controls virulence of mycobacteria , 2012, Cellular microbiology.

[12]  A. Izzo,et al.  BAT3 Regulates Mycobacterium tuberculosis Protein ESAT-6-Mediated Apoptosis of Macrophages , 2012, PloS one.

[13]  Robert Clarke,et al.  Guidelines for the use and interpretation of assays for monitoring autophagy , 2012 .

[14]  R. Brosch,et al.  Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death , 2012, PLoS pathogens.

[15]  J. Ernst,et al.  Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells. , 2012, Cell host & microbe.

[16]  Eun-Kyeong Jo,et al.  Endoplasmic Reticulum Stress Pathway-Mediated Apoptosis in Macrophages Contributes to the Survival of Mycobacterium tuberculosis , 2011, PloS one.

[17]  K. Ravichandran Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. , 2011, Immunity.

[18]  C. Sassetti,et al.  Mycobacterium tuberculosis Induces an Atypical Cell Death Mode to Escape from Infected Macrophages , 2011, PloS one.

[19]  G. Kaplan,et al.  Induction of ER Stress in Macrophages of Tuberculosis Granulomas , 2010, PloS one.

[20]  S. Behar,et al.  Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? , 2010, Nature Reviews Microbiology.

[21]  S. Behar,et al.  Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis , 2010, Nature Immunology.

[22]  G. Hur,et al.  Endoplasmic reticulum stress response is involved in Mycobacterium tuberculosis protein ESAT‐6‐mediated apoptosis , 2010, FEBS letters.

[23]  Jessica L Miller,et al.  The Type I NADH Dehydrogenase of Mycobacterium tuberculosis Counters Phagosomal NOX2 Activity to Inhibit TNF-α-Mediated Host Cell Apoptosis , 2010, PLoS pathogens.

[24]  W. Langdon,et al.  A TNF- and c-Cbl-dependent FLIPS-degradation pathway and its function in Mycobacterium tuberculosis–induced macrophage apoptosis , 2009, Nature Immunology.

[25]  S. Fortune,et al.  Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair , 2009, Nature Immunology.

[26]  R A Knight,et al.  Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes , 2009, Cell Death and Differentiation.

[27]  A. Cooper,et al.  Cell-mediated immune responses in tuberculosis. , 2009, Annual review of immunology.

[28]  M. Peters-Golden,et al.  Efferocytosis impairs pulmonary macrophage and lung antibacterial function via PGE2/EP2 signaling , 2009, The Journal of experimental medicine.

[29]  L. Ramakrishnan,et al.  The Role of the Granuloma in Expansion and Dissemination of Early Tuberculous Infection , 2009, Cell.

[30]  M. Peters-Golden,et al.  Eff erocytosis impairs pulmonary macrophage and lung antibacterial function via PGE 2 / EP 2 signaling , 2009 .

[31]  Jun Liu,et al.  Evidence for Pore Formation in Host Cell Membranes by ESX-1-Secreted ESAT-6 and Its Role in Mycobacterium marinum Escape from the Vacuole , 2008, Infection and Immunity.

[32]  K. Rock,et al.  How dying cells alert the immune system to danger , 2008, Nature Reviews Immunology.

[33]  J. Ernst,et al.  Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs , 2008, The Journal of experimental medicine.

[34]  T. Vanden Berghe,et al.  Methods for distinguishing apoptotic from necrotic cells and measuring their clearance. , 2008, Methods in enzymology.

[35]  Suzanne Cory,et al.  Bcl-2-regulated apoptosis: mechanism and therapeutic potential. , 2007, Current opinion in immunology.

[36]  A. Leong,et al.  Apoptosis is a major cause of so-called “caseous necrosis” in mycobacterial granulomas in HIV-infected patients , 2007, Journal of Clinical Pathology.

[37]  Bing Chen,et al.  Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. , 2007, The Journal of clinical investigation.

[38]  Peter J. Peters,et al.  M. tuberculosis and M. leprae Translocate from the Phagolysosome to the Cytosol in Myeloid Cells , 2007, Cell.

[39]  S. Cole,et al.  ESAT-6 from Mycobacterium tuberculosis Dissociates from Its Putative Chaperone CFP-10 under Acidic Conditions and Exhibits Membrane-Lysing Activity , 2007, Journal of bacteriology.

[40]  S. Morris,et al.  The ESAT6 protein of Mycobacterium tuberculosis induces apoptosis of macrophages by activating caspase expression , 2007, Cellular microbiology.

[41]  T. Fujimura,et al.  Involvement of Caspase-9 in the Inhibition of Necrosis of RAW 264 Cells Infected with Mycobacterium tuberculosis , 2007, Infection and Immunity.

[42]  内山 良介 Involvement of caspase-9 in the inhibition of necrosis of RAW 264 cells infected with Mycobacterium tuberculosis , 2007 .

[43]  T. Kaisho,et al.  Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages , 2007, Nature Immunology.

[44]  R. Hotchkiss,et al.  Apoptosis and caspases regulate death and inflammation in sepsis , 2006, Nature Reviews Immunology.

[45]  T. Kietzmann,et al.  The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. , 2006, Antioxidants & redox signaling.

[46]  H. Kornfeld,et al.  Macrophage Apoptosis in Response to High Intracellular Burden of Mycobacterium tuberculosis Is Mediated by a Novel Caspase-Independent Pathway1 , 2006, The Journal of Immunology.

[47]  Minjian Chen,et al.  A Mechanism of Virulence: Virulent Mycobacterium tuberculosis Strain H37Rv, but Not Attenuated H37Ra, Causes Significant Mitochondrial Inner Membrane Disruption in Macrophages Leading to Necrosis1 , 2006, The Journal of Immunology.

[48]  B. Finlay,et al.  Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens , 2006, Cell.

[49]  S. Kaufmann,et al.  Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. , 2006, Immunity.

[50]  Minjian Chen,et al.  NecrosisDisruption in Macrophages Leading to Significant Mitochondrial Inner Membrane but Not Attenuated H37Ra, Causes Strain H37Rv, Mycobacterium tuberculosis A Mechanism of Virulence: Virulent , 2006 .

[51]  Yue Zhang,et al.  Inhibition of MAPK and NF-κB Pathways Is Necessary for Rapid Apoptosis in Macrophages Infected with Yersinia1 , 2005, The Journal of Immunology.

[52]  D. Guiney The role of host cell death in Salmonella infections. , 2005, Current topics in microbiology and immunology.

[53]  D. Ojcius,et al.  Chlamydia and apoptosis: life and death decisions of an intracellular pathogen , 2004, Nature Reviews Microbiology.

[54]  P. Schierloh,et al.  Mycobacterium tuberculosis Triggers Apoptosis in Peripheral Neutrophils Involving Toll-Like Receptor 2 and p38 Mitogen Protein Kinase in Tuberculosis Patients , 2004, Infection and Immunity.

[55]  J. Engel,et al.  A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT‐6 secretion , 2004, Molecular microbiology.

[56]  D. Sherman,et al.  Individual RD1‐region genes are required for export of ESAT‐6/CFP‐10 and for virulence of Mycobacterium tuberculosis , 2004, Molecular microbiology.

[57]  R. Mondragón-Flores,et al.  Mycobacterium tuberculosis Virulence Correlates with Mitochondrial Cytochrome c Release in Infected Macrophages , 2003, Scandinavian journal of immunology.

[58]  L. Bermudez,et al.  Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells , 2003, Cellular microbiology.

[59]  S. Kaufmann,et al.  Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis , 2003, Nature Medicine.

[60]  H. Ichijo,et al.  Physiological Roles of ASK 1-Mediated Signal Transduction in Oxidative Stress-and Endoplasmic Reticulum Stress-Induced Apoptosis : Advanced Findings from ASK 1 Knockout Mice , 2003 .

[61]  Priscille Brodin,et al.  Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti , 2002, Molecular microbiology.

[62]  H. Ichijo,et al.  Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice. , 2002, Antioxidants & redox signaling.

[63]  M. Peter,et al.  Apoptosis and caspases. , 2001, Cardiology clinics.

[64]  M. Bevan,et al.  Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo , 2000, The Journal of experimental medicine.

[65]  H. Ichijo,et al.  Execution of Apoptosis Signal-regulating Kinase 1 (ASK1)-induced Apoptosis by the Mitochondria-dependent Caspase Activation* , 2000, The Journal of Biological Chemistry.

[66]  G Melino,et al.  The p53/p63/p73 family of transcription factors: overlapping and distinct functions. , 2000, Journal of cell science.

[67]  S. Falkow,et al.  Apoptosis as a common bacterial virulence strategy. , 2000, International journal of medical microbiology : IJMM.

[68]  Hardy Kornfeld,et al.  Virulent Mycobacterium tuberculosis Strains Evade Apoptosis of Infected Alveolar Macrophages1 , 2000, The Journal of Immunology.

[69]  M. Crosti,et al.  Role of antigen‐presenting cells in cross‐priming of cytotoxic T lymphocytes by apoptotic cells , 1999, Journal of leukocyte biology.

[70]  J. Keane,et al.  Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha. , 1998, Journal of immunology.

[71]  W. Rom,et al.  Copyright © 1997, American Society for Microbiology Effects of Mycobacteria on Regulation of Apoptosis in , 1997 .

[72]  G. Puzo,et al.  Differential induction of apoptosis by virulent Mycobacterium tuberculosis in resistant and susceptible murine macrophages: role of nitric oxide and mycobacterial products. , 1997, Journal of immunology.

[73]  J. Keane,et al.  Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis , 1997, Infection and immunity.

[74]  M. Prevost,et al.  Shigella flexneri induces apoptosis in infected macrophages , 1992, Nature.

[75]  S Satoh,et al.  [Endoplasmic reticulum]. , 1987, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[76]  M. Bevan Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay , 1976, The Journal of experimental medicine.

[77]  G. Palade,et al.  THE ENDOPLASMIC RETICULUM , 1956, The Journal of biophysical and biochemical cytology.