IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Host-Pathogen Dialogues in Autophagy, Apoptosis, and Necrosis during Mycobacterial Infection

  • Jin Kyung Kim (Department of Microbiology, Chungnam National University School of Medicine) ;
  • Prashanta Silwal (Department of Microbiology, Chungnam National University School of Medicine) ;
  • Eun-Kyeong Jo (Department of Microbiology, Chungnam National University School of Medicine)
  • Received : 2020.08.24
  • Accepted : 2020.10.15
  • Published : 2020.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Mycobacterium tuberculosis (Mtb) is an etiologic pathogen of human tuberculosis (TB), a serious infectious disease with high morbidity and mortality. In addition, the threat of drug resistance in anti-TB therapy is of global concern. Despite this, it remains urgent to research for understanding the molecular nature of dynamic interactions between host and pathogens during TB infection. While Mtb evasion from phagolysosomal acidification is a well-known virulence mechanism, the molecular events to promote intracellular parasitism remains elusive. To combat intracellular Mtb infection, several defensive processes, including autophagy and apoptosis, are activated. In addition, Mtb-ingested phagocytes trigger inflammation, and undergo necrotic cell death, potentially harmful responses in case of uncontrolled pathological condition. In this review, we focus on Mtb evasion from phagosomal acidification, and Mtb interaction with host autophagy, apoptosis, and necrosis. Elucidation of the molecular dialogue will shed light on Mtb pathogenesis, host defense, and development of new paradigms of therapeutics.

Keywords

Acknowledgement

We are indebted to current and past members of our laboratory for discussions and investigations that contributed to this article. This work was supported by the NRF grant funded by the Korea government (NRF-2019R1I1A1A01062086). We apologize to everyone whose work and publications could not be referenced due to space limitations.

References

  1. Liu CH, Liu H, Ge B. Innate immunity in tuberculosis: host defense vs pathogen evasion. Cell Mol Immunol 2017;14:963-975. https://doi.org/10.1038/cmi.2017.88
  2. Queiroz A, Riley LW. Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response. Rev Soc Bras Med Trop 2017;50:9-18. https://doi.org/10.1590/0037-8682-0230-2016
  3. Cooper AM. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 2009;27:393-422. https://doi.org/10.1146/annurev.immunol.021908.132703
  4. Stutz MD, Clark MP, Doerflinger M, Pellegrini M. Mycobacterium tuberculosis: rewiring host cell signaling to promote infection. J Leukoc Biol 2018;103:259-268. https://doi.org/10.1002/JLB.4MR0717-277R
  5. Poirier V, Av-Gay Y. Mycobacterium tuberculosis modulators of the macrophage's cellular events. Microbes Infect 2012;14:1211-1219. https://doi.org/10.1016/j.micinf.2012.07.001
  6. Brighenti S, Joosten SA. Friends and foes of tuberculosis: modulation of protective immunity. J Intern Med 2018;284:125-144. https://doi.org/10.1111/joim.12778
  7. Jiao Y, Sun J. Bacterial manipulation of autophagic responses in infection and inflammation. Front Immunol 2019;10:2821.
  8. Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nat Rev Immunol 2013;13:722-737. https://doi.org/10.1038/nri3532
  9. Kimmey JM, Stallings CL. Bacterial pathogens versus autophagy: implications for therapeutic interventions. Trends Mol Med 2016;22:1060-1076. https://doi.org/10.1016/j.molmed.2016.10.008
  10. Upadhyay S, Mittal E, Philips JA. Tuberculosis and the art of macrophage manipulation. Pathog Dis 2018;76:76.
  11. Krakauer T. Inflammasomes, autophagy, and cell death: the trinity of innate host defense against intracellular bacteria. Mediators Inflamm 2019;2019:2471215.
  12. Lam A, Prabhu R, Gross CM, Riesenberg LA, Singh V, Aggarwal S. Role of apoptosis and autophagy in tuberculosis. Am J Physiol Lung Cell Mol Physiol 2017;313:L218-L229. https://doi.org/10.1152/ajplung.00162.2017
  13. Huang L, Nazarova EV, Tan S, Liu Y, Russell DG. Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny. J Exp Med 2018;215:1135-1152. https://doi.org/10.1084/jem.20172020
  14. Mishra A, Surolia A. Mycobacterium tuberculosis: surviving and indulging in an unwelcoming host. IUBMB Life 2018;70:917-925. https://doi.org/10.1002/iub.1882
  15. Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, Ginsberg A, Swaminathan S, Spigelman M, Getahun H, et al. Tuberculosis. Nat Rev Dis Primers 2016;2:16076.
  16. Pagan AJ, Ramakrishnan L. The formation and function of granulomas. Annu Rev Immunol 2018;36:639-665. https://doi.org/10.1146/annurev-immunol-032712-100022
  17. Russell DG, VanderVen BC, Lee W, Abramovitch RB, Kim MJ, Homolka S, Niemann S, Rohde KH. Mycobacterium tuberculosis wears what it eats. Cell Host Microbe 2010;8:68-76. https://doi.org/10.1016/j.chom.2010.06.002
  18. Kaplan G, Post FA, Moreira AL, Wainwright H, Kreiswirth BN, Tanverdi M, Mathema B, Ramaswamy SV, Walther G, Steyn LM, et al. Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity. Infect Immun 2003;71:7099-7108. https://doi.org/10.1128/IAI.71.12.7099-7108.2003
  19. Daffe M, Crick DC, Jackson M. Genetics of capsular polysaccharides and cell envelope (glyco)lipids. Microbiol Spectr 2014;2:MGM2-MGM0021. https://doi.org/10.1128/microbiolspec.MGM2-0021-2013
  20. Brennan PJ. Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2003;83:91-97. https://doi.org/10.1016/S1472-9792(02)00089-6
  21. Groschel MI, Sayes F, Simeone R, Majlessi L, Brosch R. ESX secretion systems: mycobacterial evolution to counter host immunity. Nat Rev Microbiol 2016;14:677-691. https://doi.org/10.1038/nrmicro.2016.131
  22. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783-801. https://doi.org/10.1016/j.cell.2006.02.015
  23. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010;11:373-384. https://doi.org/10.1038/ni.1863
  24. Basu J, Shin DM, Jo EK. Mycobacterial signaling through Toll-like receptors. Front Cell Infect Microbiol 2012;2:145.
  25. Schorey JS, Schlesinger LS. Innate immune responses to tuberculosis. Microbiol Spectr 2016;4:4.
  26. Shi L, Eugenin EA, Subbian S. Immunometabolism in tuberculosis. Front Immunol 2016;7:150.
  27. Singh P, Subbian S. Harnessing the mTOR pathway for tuberculosis treatment. Front Microbiol 2018;9:70.
  28. Hmama Z, Pena-Diaz S, Joseph S, Av-Gay Y. Immunoevasion and immunosuppression of the macrophage by Mycobacterium tuberculosis. Immunol Rev 2015;264:220-232. https://doi.org/10.1111/imr.12268
  29. Meena LS, Rajni. Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv. FEBS J 2010;277:2416-2427. https://doi.org/10.1111/j.1742-4658.2010.07666.x
  30. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, Haddix PL, Collins HL, Fok AK, Allen RD, Gluck SL, Heuser J, Russell DG. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 1994;263:678-681. https://doi.org/10.1126/science.8303277
  31. Tan T, Lee WL, Alexander DC, Grinstein S, Liu J. The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation. Cell Microbiol 2006;8:1417-1429. https://doi.org/10.1111/j.1462-5822.2006.00721.x
  32. Vandal OH, Pierini LM, Schnappinger D, Nathan CF, Ehrt S. A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis. Nat Med 2008;14:849-854. https://doi.org/10.1038/nm.1795
  33. Kan-Sutton C, Jagannath C, Hunter RL Jr. Trehalose 6,6'-dimycolate on the surface of Mycobacterium tuberculosis modulates surface marker expression for antigen presentation and costimulation in murine macrophages. Microbes Infect 2009;11:40-48. https://doi.org/10.1016/j.micinf.2008.10.006
  34. Wei L, Wu J, Liu H, Yang H, Rong M, Li D, Zhang P, Han J, Lai R. A mycobacteriophage-derived trehalose-6,6'-dimycolate-binding peptide containing both antimycobacterial and anti-inflammatory abilities. FASEB J 2013;27:3067-3077. https://doi.org/10.1096/fj.13-227454
  35. Patin EC, Geffken AC, Willcocks S, Leschczyk C, Haas A, Nimmerjahn F, Lang R, Ward TH, Schaible UE. Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling. PLoS One 2017;12:e0174973.
  36. McMullen AM, Hwang SA, O'Shea K, Aliru ML, Actor JK. Evidence for a unique species-specific hypersensitive epitope in Mycobacterium tuberculosis derived cord factor. Tuberculosis (Edinb) 2013;93 Suppl:S88-S93. https://doi.org/10.1016/S1472-9792(13)70017-9
  37. Kissing S, Saftig P, Haas A. Vacuolar ATPase in phago(lyso)some biology. Int J Med Microbiol 2018;308:58-67. https://doi.org/10.1016/j.ijmm.2017.08.007
  38. Kissing S, Hermsen C, Repnik U, Nesset CK, von Bargen K, Griffiths G, Ichihara A, Lee BS, Schwake M, De Brabander J, et al. Vacuolar ATPase in phagosome-lysosome fusion. J Biol Chem 2015;290:14166-14180. https://doi.org/10.1074/jbc.M114.628891
  39. Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y. Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A 2011;108:19371-19376. https://doi.org/10.1073/pnas.1109201108
  40. Koliwer-Brandl H, Knobloch P, Barisch C, Welin A, Hanna N, Soldati T, Hilbi H. Distinct Mycobacterium marinum phosphatases determine pathogen vacuole phosphoinositide pattern, phagosome maturation, and escape to the cytosol. Cell Microbiol 2019;21:e13008.
  41. Sullivan JT, Young EF, McCann JR, Braunstein M. The Mycobacterium tuberculosis SecA2 system subverts phagosome maturation to promote growth in macrophages. Infect Immun 2012;80:996-1006. https://doi.org/10.1128/IAI.05987-11
  42. Zulauf KE, Sullivan JT, Braunstein M. The SecA2 pathway of Mycobacterium tuberculosis exports effectors that work in concert to arrest phagosome and autophagosome maturation. PLoS Pathog 2018;14:e1007011.
  43. Queval CJ, Song OR, Carralot JP, Saliou JM, Bongiovanni A, Deloison G, Deboosere N, Jouny S, Iantomasi R, Delorme V, et al. Mycobacterium tuberculosis controls phagosomal acidification by targeting CISHmediated signaling. Cell Reports 2017;20:3188-3198. https://doi.org/10.1016/j.celrep.2017.08.101
  44. Kolonko M, Geffken AC, Blumer T, Hagens K, Schaible UE, Hagedorn M. WASH-driven actin polymerization is required for efficient mycobacterial phagosome maturation arrest. Cell Microbiol 2014;16:232-246. https://doi.org/10.1111/cmi.12217
  45. Jung JY, Robinson CM. IL-12 and IL-27 regulate the phagolysosomal pathway in mycobacteria-infected human macrophages. Cell Commun Signal 2014;12:16.
  46. Chun Y, Kim J. Autophagy: an essential degradation program for cellular homeostasis and life. Cells 2018;7:278.
  47. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451:1069-1075. https://doi.org/10.1038/nature06639
  48. Kraft C, Reggiori F, Peter M. Selective types of autophagy in yeast. Biochim Biophys Acta 2009;1793:1404-1412. https://doi.org/10.1016/j.bbamcr.2009.02.006
  49. Khaminets A, Behl C, Dikic I. Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol 2016;26:6-16.  https://doi.org/10.1016/j.tcb.2015.08.010
  50. Cemma M, Brumell JH. Interactions of pathogenic bacteria with autophagy systems. Curr Biol 2012;22:R540-R545. https://doi.org/10.1016/j.cub.2012.06.001
  51. Huang J, Brumell JH. Bacteria-autophagy interplay: a battle for survival. Nat Rev Microbiol 2014;12:101-114. https://doi.org/10.1038/nrmicro3160
  52. Collins AC, Cai H, Li T, Franco LH, Li XD, Nair VR, Scharn CR, Stamm CE, Levine B, Chen ZJ, et al. Cyclic GMP-AMP synthase is an innate immune DNA sensor for Mycobacterium tuberculosis. Cell Host Microbe 2015;17:820-828. https://doi.org/10.1016/j.chom.2015.05.005
  53. Watson RO, Manzanillo PS, Cox JS. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 2012;150:803-815. https://doi.org/10.1016/j.cell.2012.06.040
  54. Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G, Rae CS, Schneider DS, Nakamura K, Shiloh MU, Cox JS. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature 2013;501:512-516. https://doi.org/10.1038/nature12566
  55. Franco LH, Nair VR, Scharn CR, Xavier RJ, Torrealba JR, Shiloh MU, Levine B. The ubiquitin ligase Smurf1 functions in selective autophagy of Mycobacterium tuberculosis and anti-tuberculous host defense. Cell Host Microbe 2017;21:59-72. https://doi.org/10.1016/j.chom.2016.11.002
  56. Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, Komisopoulou E, Kelly-Scumpia K, Chun R, Iyer SS, et al. Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science 2013;339:1448-1453. https://doi.org/10.1126/science.1233665
  57. Donovan ML, Schultz TE, Duke TJ, Blumenthal A. Type I interferons in the pathogenesis of tuberculosis: molecular drivers and immunological consequences. Front Immunol 2017;8:1633.
  58. Sakowski ET, Koster S, Portal Celhay C, Park HS, Shrestha E, Hetzenecker SE, Maurer K, Cadwell K, Philips JA. Ubiquilin 1 promotes IFN-γ-induced xenophagy of Mycobacterium tuberculosis. PLoS Pathog 2015;11:e1005076.
  59. Rovetta AI, Pena D, Hernandez Del Pino RE, Recalde GM, Pellegrini J, Bigi F, Musella RM, Palmero DJ, Gutierrez M, Colombo MI, et al. IFNG-mediated immune responses enhance autophagy against Mycobacterium tuberculosis antigens in patients with active tuberculosis. Autophagy 2014;10:2109-2121. https://doi.org/10.4161/15548627.2014.981791
  60. Chauhan S, Kumar S, Jain A, Ponpuak M, Mudd MH, Kimura T, Choi SW, Peters R, Mandell M, Bruun JA, et al. Trims and Galectins globally cooperate and TRIM16 and Galectin-3 co-direct autophagy in endomembrane damage homeostasis. Dev Cell 2016;39:13-27. https://doi.org/10.1016/j.devcel.2016.08.003
  61. Jia J, Abudu YP, Claude-Taupin A, Gu Y, Kumar S, Choi SW, Peters R, Mudd MH, Allers L, Salemi M, et al. Galectins control mTOR in response to endomembrane damage. Mol Cell 2018;70:120-135.e8. https://doi.org/10.1016/j.molcel.2018.03.009
  62. Wong KW. The role of ESX-1 in Mycobacterium tuberculosis pathogenesis. Microbiol Spectr 2017;5:TBTB2-0001-2015.
  63. Behura A, Mishra A, Chugh S, Mawatwal S, Kumar A, Manna D, Mishra A, Singh R, Dhiman R. ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages. J Infect 2019;79:139-152. https://doi.org/10.1016/j.jinf.2019.06.001
  64. Shin DM, Jeon BY, Lee HM, Jin HS, Yuk JM, Song CH, Lee SH, Lee ZW, Cho SN, Kim JM, et al. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling. PLoS Pathog 2010;6:e1001230.
  65. Koster S, Upadhyay S, Chandra P, Papavinasasundaram K, Yang G, Hassan A, Grigsby SJ, Mittal E, Park HS, Jones V, et al. Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA. Proc Natl Acad Sci U S A 2017;114:E8711-E8720. https://doi.org/10.1073/pnas.1707792114
  66. Wellcome Trust Case Control Consortium, Craddock N, Hurles ME, Cardin N, Pearson RD, Plagnol V, Robson S, Vukcevic D, Barnes C, Conrad DF, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature 2010;464:713-720. https://doi.org/10.1038/nature08979
  67. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661-678. https://doi.org/10.1038/nature05911
  68. Brest P, Lapaquette P, Souidi M, Lebrigand K, Cesaro A, Vouret-Craviari V, Mari B, Barbry P, Mosnier JF, Hebuterne X, et al. A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Nat Genet 2011;43:242-245. https://doi.org/10.1038/ng.762
  69. McCarroll SA, Huett A, Kuballa P, Chilewski SD, Landry A, Goyette P, Zody MC, Hall JL, Brant SR, Cho JH, et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet 2008;40:1107-1112. https://doi.org/10.1038/ng.215
  70. Chauhan S, Mandell MA, Deretic V. IRGM governs the core autophagy machinery to conduct antimicrobial defense. Mol Cell 2015;58:507-521. https://doi.org/10.1016/j.molcel.2015.03.020
  71. Kimmey JM, Huynh JP, Weiss LA, Park S, Kambal A, Debnath J, Virgin HW, Stallings CL. Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature 2015;528:565-569. https://doi.org/10.1038/nature16451
  72. Castillo EF, Dekonenko A, Arko-Mensah J, Mandell MA, Dupont N, Jiang S, Delgado-Vargas M, Timmins GS, Bhattacharya D, Yang H, et al. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci U S A 2012;109:E3168-E3176. https://doi.org/10.1073/pnas.1210500109
  73. Pahari S, Negi S, Aqdas M, Arnett E, Schlesinger LS, Agrewala JN. Induction of autophagy through CLEC4E in combination with TLR4: an innovative strategy to restrict the survival of Mycobacterium tuberculosis. Autophagy 2020;16:1021-1043. https://doi.org/10.1080/15548627.2019.1658436
  74. Kim TS, Jin YB, Kim YS, Kim S, Kim JK, Lee HM, Suh HW, Choe JH, Kim YJ, Koo BS, et al. SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions. Autophagy 2019;15:1356-1375. https://doi.org/10.1080/15548627.2019.1582743
  75. Bruns H, Stenger S. New insights into the interaction of Mycobacterium tuberculosis and human macrophages. Future Microbiol 2014;9:327-341. https://doi.org/10.2217/fmb.13.164
  76. Mohareer K, Asalla S, Banerjee S. Cell death at the cross roads of host-pathogen interaction in Mycobacterium tuberculosis infection. Tuberculosis (Edinb) 2018;113:99-121. https://doi.org/10.1016/j.tube.2018.09.007
  77. Zhai W, Wu F, Zhang Y, Fu Y, Liu Z. The immune escape mechanisms of Mycobacterium tuberculosis. Int J Mol Sci 2019;20:340.
  78. Behar SM, Briken V. Apoptosis inhibition by intracellular bacteria and its consequence on host immunity. Curr Opin Immunol 2019;60:103-110. https://doi.org/10.1016/j.coi.2019.05.007
  79. Keane J, Remold HG, Kornfeld H. Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol 2000;164:2016-2020. https://doi.org/10.4049/jimmunol.164.4.2016
  80. Balcewicz-Sablinska MK, Keane J, Kornfeld H, Remold HG. Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha. J Immunol 1998;161:2636-2641. https://doi.org/10.4049/jimmunol.161.5.2636
  81. Grover S, Sharma T, Singh Y, Kohli S, P M, Singh A, Semmler T, Wieler LH, Tedin K, Ehtesham NZ, et al. The PGRS domain of Mycobacterium tuberculosis PE_PGRS protein Rv0297 is involved in endoplasmic reticulum stress-mediated apoptosis through Toll-like receptor 4. MBio 2018;9:e01017-18. https://doi.org/10.1128/mBio.01017-18
  82. Lin J, Chang Q, Dai X, Liu D, Jiang Y, Dai Y. Early secreted antigenic target of 6-kDa of Mycobacterium tuberculosis promotes caspase-9/caspase-3-mediated apoptosis in macrophages. Mol Cell Biochem 2019;457:179-189. https://doi.org/10.1007/s11010-019-03522-x
  83. Yang S, Li F, Jia S, Zhang K, Jiang W, Shang Y, Chang K, Deng S, Chen M. Early secreted antigen ESAT-6 of Mycobacterium Tuberculosis promotes apoptosis of macrophages via targeting the microRNA155-SOCS1 interaction. Cell Physiol Biochem 2015;35:1276-1288. https://doi.org/10.1159/000373950
  84. Augenstreich J, Arbues A, Simeone R, Haanappel E, Wegener A, Sayes F, Le Chevalier F, Chalut C, Malaga W, Guilhot C, et al. ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis. Cell Microbiol 2017;19:e12726.
  85. Wang L, Zuo M, Chen H, Liu S, Wu X, Cui Z, Yang H, Liu H, Ge B. Mycobacterium tuberculosis lipoprotein MPT83 induces apoptosis of infected macrophages by activating the TLR2/p38/COX-2 signaling pathway. J Immunol 2017;198:4772-4780. https://doi.org/10.4049/jimmunol.1700030
  86. Su H, Zhu S, Zhu L, Huang W, Wang H, Zhang Z, Xu Y. Recombinant lipoprotein rv1016c derived from Mycobacterium tuberculosis is a TLR-2 ligand that induces macrophages apoptosis and inhibits MHC II antigen processing. Front Cell Infect Microbiol 2016;6:147.
  87. Lim YJ, Choi JA, Lee JH, Choi CH, Kim HJ, Song CH. Mycobacterium tuberculosis 38-kDa antigen induces endoplasmic reticulum stress-mediated apoptosis via toll-like receptor 2/4. Apoptosis 2015;20:358-370. https://doi.org/10.1007/s10495-014-1080-2
  88. Halder P, Kumar R, Jana K, Chakraborty S, Ghosh Z, Kundu M, Basu J. Gene expression profiling of Mycobacterium tuberculosis Lipoarabinomannan-treated macrophages: a role of the Bcl-2 family member A1 in inhibition of apoptosis in mycobacteria-infected macrophages. IUBMB Life 2015;67:726-736. https://doi.org/10.1002/iub.1430
  89. Joseph S, Yuen A, Singh V, Hmama Z. Mycobacterium tuberculosis Cpn60.2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin. Biol Open 2017;6:481-488.
  90. Yang W, Deng W, Zeng J, Ren S, Ali MK, Gu Y, Li Y, Xie J. Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M. smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis. Apoptosis 2017;22:502-509. https://doi.org/10.1007/s10495-016-1336-0
  91. Li F, Feng L, Jin C, Wu X, Fan L, Xiong S, Dong Y. LpqT improves mycobacteria survival in macrophages by inhibiting TLR2 mediated inflammatory cytokine expression and cell apoptosis. Tuberculosis (Edinb) 2018;111:57-66. https://doi.org/10.1016/j.tube.2018.05.007
  92. Paik S, Choi S, Lee KI, Back YW, Son YJ, Jo EK, Kim HJ. Mycobacterium tuberculosis acyl carrier protein inhibits macrophage apoptotic death by modulating the reactive oxygen species/c-Jun N-terminal kinase pathway. Microbes Infect 2019;21:40-49. https://doi.org/10.1016/j.micinf.2018.06.005
  93. Leu JS, Chen ML, Chang SY, Yu SL, Lin CW, Wang H, Chen WC, Chang CH, Wang JY, Lee LN, et al. Sp110b controls host immunity and susceptibility to tuberculosis. Am J Respir Crit Care Med 2017;195:369-382. https://doi.org/10.1164/rccm.201601-0103OC
  94. Francis RJ, Butler RE, Stewart GR. Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx, necrosis and neutrophil extracellular trap formation. Cell Death Dis 2014;5:e1474.
  95. Niazi MK, Dhulekar N, Schmidt D, Major S, Cooper R, Abeijon C, Gatti DM, Kramnik I, Yener B, Gurcan M, et al. Lung necrosis and neutrophils reflect common pathways of susceptibility to Mycobacterium tuberculosis in genetically diverse, immune-competent mice. Dis Model Mech 2015;8:1141-1153.
  96. Marzo E, Vilaplana C, Tapia G, Diaz J, Garcia V, Cardona PJ. Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis. Tuberculosis (Edinb) 2014;94:55-64. https://doi.org/10.1016/j.tube.2013.09.004
  97. Dallenga T, Repnik U, Corleis B, Eich J, Reimer R, Griffiths GW, Schaible UE. M. tuberculosis-induced necrosis of infected neutrophils promotes bacterial growth following phagocytosis by macrophages. Cell Host Microbe 2017;22:519-530.e3. https://doi.org/10.1016/j.chom.2017.09.003
  98. Lerner TR, Borel S, Greenwood DJ, Repnik U, Russell MR, Herbst S, Jones ML, Collinson LM, Griffiths G, Gutierrez MG. Mycobacterium tuberculosis replicates within necrotic human macrophages. J Cell Biol 2017;216:583-594. https://doi.org/10.1083/jcb.201603040
  99. Mahamed D, Boulle M, Ganga Y, Mc Arthur C, Skroch S, Oom L, Catinas O, Pillay K, Naicker M, Rampersad S, et al. Correction: intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells. eLife 2017;6:e28205. 
  100. Filio-Rodriguez G, Estrada-Garcia I, Arce-Paredes P, Moreno-Altamirano MM, Islas-Trujillo S, Ponce-Regalado MD, Rojas-Espinosa O. In vivo induction of neutrophil extracellular traps by Mycobacterium tuberculosis in a guinea pig model. Innate Immun 2017;23:625-637. https://doi.org/10.1177/1753425917732406
  101. Rybniker J, Chen JM, Sala C, Hartkoorn RC, Vocat A, Benjak A, Boy-Rottger S, Zhang M, Szekely R, Greff Z, et al. Anticytolytic screen identifies inhibitors of mycobacterial virulence protein secretion. Cell Host Microbe 2014;16:538-548. https://doi.org/10.1016/j.chom.2014.09.008
  102. Peng X, Luo T, Zhai X, Zhang C, Suo J, Ma P, Wang C, Bao L. PPE11 of Mycobacterium tuberculosis can alter host inflammatory response and trigger cell death. Microb Pathog 2019;126:45-55. https://doi.org/10.1016/j.micpath.2018.10.031
  103. Li Z, Liu H, Li H, Dang G, Cui Z, Song N, Wang Q, Liu S, Chen L. PE17 protein from Mycobacterium tuberculosis enhances Mycobacterium smegmatis survival in macrophages and pathogenicity in mice. Microb Pathog 2019;126:63-73. https://doi.org/10.1016/j.micpath.2018.10.030
  104. Gopalakrishnan A, Dietzold J, Verma S, Bhagavathula M, Salgame P. Toll-like receptor 2 prevents neutrophil-driven immunopathology during infection with Mycobacterium tuberculosis by curtailing CXCL5 production. Infect Immun 2019;87:e00760-18.
  105. Simeone R, Bottai D, Frigui W, Majlessi L, Brosch R. ESX/type VII secretion systems of mycobacteria: insights into evolution, pathogenicity and protection. Tuberculosis (Edinb) 2015;95 Suppl 1:S150-S154. https://doi.org/10.1016/j.tube.2015.02.019
  106. Nouailles G, Dorhoi A, Koch M, Zerrahn J, Weiner J 3rd, Fae KC, Arrey F, Kuhlmann S, Bandermann S, Loewe D, et al. CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J Clin Invest 2014;124:1268-1282. https://doi.org/10.1172/JCI72030
  107. Lombard R, Doz E, Carreras F, Epardaud M, Le Vern Y, Buzoni-Gatel D, Winter N. IL-17RA in non-hematopoietic cells controls CXCL-1 and 5 critical to recruit neutrophils to the lung of mycobacteria-infected mice during the adaptive immune response. PLoS One 2016;11:e0149455.
  108. Dorhoi A, Yeremeev V, Nouailles G, Weiner J 3rd, Jorg S, Heinemann E, Oberbeck-Muller D, Knaul JK, Vogelzang A, Reece ST, et al. Type I IFN signaling triggers immunopathology in tuberculosis-susceptible mice by modulating lung phagocyte dynamics. Eur J Immunol 2014;44:2380-2393. https://doi.org/10.1002/eji.201344219
  109. Pagan AJ, Ramakrishnan L. Immunity and immunopathology in the tuberculous granuloma. Cold Spring Harb Perspect Med 2014;5:a018499.