Targeting apoptosis pathways in infections

Journal of Leukocyte Biology

Volumn 103, Issue 2, 2018, Pages 275-285

  Naderer, Thomas ^a   Fulcher, Maria Cecilia ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

BCL 2; caspase; cell death; inflammation; Legionella; mitochondria

Indexed keywords

APOPTOSIS; CANCER CELL; CELL DEATH; CELL FATE; HOST CELL; HOST PATHOGEN INTERACTION; INFECTION; INFECTIOUS AGENT; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; COMMUNICABLE DISEASE; DISEASE MODEL; DRUG EFFECT; HUMAN; IMMUNE SYSTEM; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY;

APOPTOSIS REGULATORY PROTEIN; PROTEIN BCL 2;

ANIMALS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; COMMUNICABLE DISEASES; DISEASE MODELS, ANIMAL; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNE SYSTEM; MICE, KNOCKOUT; MITOCHONDRIA; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 85040963891     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/JLB.4MR0717-286R     Document Type: Review

References (139)

1. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15:49–63.
2. Lindsten T, Ross AJ, King A, et al. The combined functions of proapoptotic Bcl-2 family members BAK and BAX are essential for normal development of multiple tissues. Mol Cell. 2000;6:1389–1399.
3. Kristiansen M, Ham J. Programmed cell death during neuronal development: the sympathetic neuron model. Cell Death Differ. 2014;21:1025–1035.
4. Dekkers MP, Barde YA. Developmental biology. Programmed cell death in neuronal development. Science. 2013;340:39–41.
5. Knudson CM, Tung KS, Tourtellotte WG, Brown GA, Korsmeyer SJ. BAX-deficient mice with lymphoid hyperplasia and male germ cell death. Science. 1995;270:96–99.
6. Chow SH, Deo P, Naderer T. Macrophage cell death in microbial infections. Cell Microbiol. 2016;18:466–474.
7. Jorgensen I, Rayamajhi M, Miao EA. Programmed cell death as a defence against infection. Nat Rev Immunol. 2017;17:151–164.
8. Vince JE, Silke J. The intersection of cell death and inflammasome activation. Cell Mol Life Sci. 2016;73:2349–2367.
9. Wallach D, Kang TB, Dillon CP, Green DR. Programmed necrosis in inflammation: toward identification of the effector molecules. Science. 2016;352. doi: 10.1126/science.aaf2154.
10. Atkin-Smith GK, Poon IK. Disassembly of the dying: mechanisms and functions. Trends Cell Biol. 2017;27:151–162.
11. Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol. 2014;14:166–180.
12. McDonnell TJ, Deane N, Platt FM, et al. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989;57:79–88.
13. Strasser A, Harris AW, Cory S. Bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991;67:889–899.
14. Strasser A, Whittingham S, Vaux DL, et al. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci USA. 1991;88:8661–8665.
15. Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68:3421–3428.
16. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435:677–681.
17. Roberts AW, Stilgenbauer S, Seymour JF, Huang DC. Venetoclax in patients with previously treated chronic lymphocytic leukemia. Clin Cancer Res. 2017;23:4527–4533.
18. Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19:202–208.
19. Carrington EM, Vikstrom IB, Light A, et al. BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs. Proc Natl Acad Sci USA. 2010;107:10967–10971.
20. Bardwell PD, Gu J, McCarthy D, et al. The Bcl-2 family antagonist ABT-737 significantly inhibits multiple animal models of autoimmunity. J Immunol. 2009;182:7482–7489.
21. Gamradt P, Xu Y, Gratz N, et al. The influence of programmed cell death in myeloid cells on host resilience to infection with Legionella pneumophila or Streptococcus pyogenes. PLoS Pathogens. 2016;12:e1006032.
22. Pierson W, Cauwe B, Policheni A, et al. Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3(+) regulatory T cells. Nat Immunol. 2013;14:959–965.
23. Winau F, Kaufmann SH, Schaible UE. Apoptosis paves the detour path for CD8 T cell activation against intracellular bacteria. Cell Microbiol. 2004;6:599–607.
24. White MJ, McArthur K, Metcalf D, et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell. 2014;159:1549–1562.
25. Rongvaux A, Jackson R, Harman CC, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563–1577.
26. Rogers C, Fernandes-Alnemri T, Mayes L, Alnemri D, Cingolani G, Alnemri ES. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat Commun. 2017;8:14128.
27. Wang Y, Gao W, Shi X, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547:99–103.
28. Behar SM, Divangahi M, Remold HG. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy?. Nat Rev Microbiol. 2010;8:668–674.
29. Albert ML. Death-defying immunity: do apoptotic cells influence antigen processing and presentation?. Nat Rev Immunol. 2004;4:223–231.
30. Martin CJ, Peters KN, Behar SM. Macrophages clean up: efferocytosis and microbial control. Curr Opin Microbiol. 2014;17:17–23.
31. Nogueira CV, Lindsten T, Jamieson AM, et al. Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila. PLoS Pathogens. 2009;5:e1000478.
32. Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15:388–400.
33. Wei MC, Zong WX, Cheng EH, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001;292:727–730.
34. Czabotar PE, Westphal D, Dewson G, et al. BAX crystal structures reveal how BH3 domains activate BAX and nucleate its oligomerization to induce apoptosis. Cell. 2013;152:519–531.
35. Strasser A, Cory S, Adams JM. Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J. 2011;30:3667–3683.
36. Grosse L, Wurm CA, Bruser C, Neumann D, Jans DC, Jakobs S. BAX assembles into large ring-like structures remodeling the mitochondrial outer membrane in apoptosis. EMBO J. 2016;35:402–413.
37. Uren RT, O'Hely M, Iyer S, et al. Disordered clusters of BAK dimers rupture mitochondria during apoptosis. Elife. 2017;6:e19944.
38. O'Neill KL, Huang K, Zhang J, Chen Y, Luo X. Inactivation of prosurvival Bcl-2 proteins activates BAX/BAK through the outer mitochondrial membrane. Genes Dev. 2016;30:973–988.
39. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9:47–59.
40. Llambi F, Moldoveanu T, Tait SW, et al. A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol Cell. 2011;44:517–531.
41. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996;86:147–157.
42. Li K, Li Y, Shelton JM, et al. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell. 2000;101:389–399.
43. Hakem R, Hakem A, Duncan GS, et al. Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell. 1998;94:339–352.
44. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. APAF-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell. 1997;90:405–413.
45. Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 2000;102:33–42.
46. Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000;102:43–53.
47. Yu SW, Wang H, Poitras MF, et al. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science. 2002;297:259–263.
48. Kuida K, Haydar TF, Kuan CY, et al. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell. 1998;94:325–337.
49. Margaroli C, Oberle S, Lavanchy C, et al. Role of proapoptotic BH3-only proteins in Listeria monocytogenes infection. Eur J Immunol. 2016;46:1427–1437.
50. Marriott HM, Bingle CD, Read RC, et al. Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance. J Clin Invest. 2005;115:359–368.
51. Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 2012;119:651–665.
52. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 1975;72:3666–3670.
53. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 2001;11:372–377.
54. Beutler B, Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986;320:584–588.
55. Hsu H, Shu HB, Pan MG, Goeddel DV. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell. 1996;84:299–308.
56. Li H, Zhu H, Xu CJ, Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998;94:491–501.
57. Feltham R, Vince JE, Lawlor KE. Caspase-8: not so silently deadly. Clin Transl Immunology. 2017;6:e124.
58. Kang S, Fernandes-Alnemri T, Rogers C, et al. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nat Commun. 2015;6:7515.
59. Vince JE, Wong WW, Gentle I, et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity. 2012;36:215–227.
60. Lawlor KE, Khan N, Mildenhall A, et al. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun. 2015;6:6282.
61. Sagulenko V, Thygesen SJ, Sester DP, et al. AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death Differ. 2013;20:1149–1160.
62. Mascarenhas DPA, Cerqueira DM, Pereira MSF, et al. Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome. PLoS Pathogens. 2017;13:e1006502.
63. He WT, Wan H, Hu L, et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell Res. 2015;25:1285–1298.
64. Oberst A, Dillon CP, Weinlich R, et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471:363–367.
65. Abu-Zant A, Jones S, Asare R, et al. Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila. Cell Microbiol. 2007;9:246–264.
66. Losick VP, Isberg RR. NF-kappaB translocation prevents host cell death after low-dose challenge by Legionella pneumophila. J Exp Med. 2006;203:2177–2189.
67. Banga S, Gao P, Shen X, et al. Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death members of the Bcl2 protein family. Proc Natl Acad Sci USA. 2007;104:5121–5126.
68. Speir M, Vogrin A, Seidi A, et al. Legionella pneumophila strain 130b evades macrophage cell death independent of the effector SidF in the absence of Flagellin. Front Cell Infect Microbiol. 2017;7:35.
69. Speir M, Lawler K, Glaser S, et al. Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis. Nat Microbiol. 2016;1:15034.
70. Adams KW, Cooper GM. Rapid turnover of mcl-1 couples translation to cell survival and apoptosis. J Biol Chem. 2007;282:6192–6200.
71. Fischer SF, Vier J, Kirschnek S, et al. Chlamydia inhibit host cell apoptosis by degradation of proapoptotic BH3-only proteins. J Exp Med. 2004;200:905–916.
72. Pirbhai M, Dong F, Zhong Y, Pan KZ, Zhong G. The secreted protease factor CPAF is responsible for degrading pro-apoptotic BH3-only proteins in Chlamydia trachomatis-infected cells. J Biol Chem. 2006;281:31495–31501.
73. Dong F, Pirbhai M, Xiao Y, Zhong Y, Wu Y, Zhong G. Degradation of the proapoptotic proteins BIK, PUMA, and BIM with Bcl-2 domain 3 homology in Chlamydia trachomatis-infected cells. Infect Immun. 2005;73:1861–1864.
74. Verbeke P, Welter-Stahl L, Ying S, et al. Recruitment of BAD by the Chlamydia trachomatis vacuole correlates with host-cell survival. PLoS Pathogens. 2006;2:e45.
75. Rajalingam K, Sharma M, Lohmann C, et al. Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells. PLoS One. 2008;3:e3102.
76. Sharma M, Machuy N, Bohme L, et al. HIF-1alpha is involved in mediating apoptosis resistance to Chlamydia trachomatis-infected cells. Cell Microbiol. 2011;13:1573–1585.
77. Fischer A, Harrison KS, Ramirez Y, et al. Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense. Elife. 2017;6:pii: e21465.
78. Wang Q, Liu S, Tang Y, Liu Q, Yao Y. MPT64 protein from Mycobacterium tuberculosis inhibits apoptosis of macrophages through NF-kB-miRNA21-Bcl-2 pathway. PLoS One. 2014;9:e100949.
79. Sly LM, Hingley-Wilson SM, Reiner NE, McMaster WR. Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1. J Immunol. 2003;170:430–437.
80. Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci USA. 1992;89:7742–7746.
81. Sarid R, Sato T, Bohenzky RA, Russo JJ, Chang Y. Kaposi's sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat Med. 1997;3:293–298.
82. Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A. Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci USA. 1993;90:8479–8483.
83. Coleman CB, McGraw JE, Feldman ER, et al. A gammaherpesvirus Bcl-2 ortholog blocks B cell receptor-mediated apoptosis and promotes the survival of developing B cells in vivo. PLoS Pathogens. 2014;10:e1003916.
84. Gallo A, Lampe M, Gunther T, Brune W. The viral Bcl-2 homologs of Kaposi's sarcoma-associated herpesvirus and rhesus rhadinovirus share an essential role for viral replication. J Virol. 2017;91. doi: 10.1128/JVI.01875-16.
85. Kvansakul M, van Delft MF, Lee EF, et al. A structural viral mimic of prosurvival Bcl-2: a pivotal role for sequestering proapoptotic BAX and BAK. Mol Cell. 2007;25:933–942.
86. Banadyga L, Lam SC, Okamoto T, Kvansakul M, Huang DC, Barry M. Deerpox virus encodes an inhibitor of apoptosis that regulates BAK and BAX. J Virol. 2011;85:1922–1934.
87. Okamoto T, Campbell S, Mehta N, et al. Sheeppox virus SPPV14 encodes a Bcl-2-like cell death inhibitor that counters a distinct set of mammalian proapoptotic proteins. J Virol. 2012;86:11501–11511.
88. Galluzzi L, Brenner C, Morselli E, Touat Z, Kroemer G. Viral control of mitochondrial apoptosis. PLoS Pathogens. 2008;4:e1000018.
89. Huang Q, Deveraux QL, Maeda S, et al. Evolutionary conservation of apoptosis mechanisms: lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9. Proc Natl Acad Sci USA. 2000;97:1427–1432.
90. Thome M, Schneider P, Hofmann K, et al. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature. 1997;386:517–521.
91. Mesri EA, Cesarman E, Boshoff C. Kaposi's sarcoma and its associated herpesvirus. Nat Rev Cancer. 2010;10:707–719.
92. Best SM. Viral subversion of apoptotic enzymes: escape from death row. Annu Rev Microbiol. 2008;62:171–192.
93. Blasche S, Mortl M, Steuber H, et al. The E. coli effector protein NleF is a caspase inhibitor. PLoS One. 2013;8:e58937.
94. Pollock GL, Oates CV, Giogha C, et al. Distinct roles of the antiapoptotic effectors NleB and NleF from enteropathogenic Escherichia coli. Infect Immun. 2017;85. http://doi.org/10.1128/IAI.01071-16.
95. Pallett MA, Crepin VF, Serafini N, et al. Bacterial virulence factor inhibits caspase-4/11 activation in intestinal epithelial cells. Mucosal Immunol. 2017;10:602–612.
96. Li S, Zhang L, Yao Q, et al. Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains. Nature. 2013;501:242–246.
97. Pearson JS, Giogha C, Ong SY, et al. A type III effector antagonizes death receptor signalling during bacterial gut infection. Nature. 2013;501:247–251.
98. Pearson JS, Giogha C, Muhlen S, et al. EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation. Nat Microbiol. 2017;2:16258.
99. Bielaszewska M, Ruter C, Kunsmann L, et al. Enterohemorrhagic Escherichia coli hemolysin employs outer membrane vesicles to target mitochondria and cause endothelial and epithelial apoptosis. PLoS Pathogens. 2013;9:e1003797.
100. Bielaszewska M, Ruter C, Bauwens A, et al. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: intracellular delivery, trafficking and mechanisms of cell injury. PLoS Pathogens. 2017;13:e1006159.
101. Muller A, Rassow J, Grimm J, Machuy N, Meyer TF, Rudel T. VDAC and the bacterial porin PorB of Neisseria gonorrhoeae share mitochondrial import pathways. EMBO J. 2002;21:1916–1929.
102. Jiang JH, Davies JK, Lithgow T, Strugnell RA, Gabriel K. Targeting of Neisserial PorB to the mitochondrial outer membrane: an insight on the evolution of beta-barrel protein assembly machines. Mol Microbiol. 2011;82:976–987.
103. Massari P, Ho Y, Wetzler LM. Neisseria meningitidis porin PorB interacts with mitochondria and protects cells from apoptosis. Proc Natl Acad Sci USA. 2000;97:9070–9075.
104. Kozjak-Pavlovic V, Dian-Lothrop EA, Meinecke M, et al. Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis. PLoS Pathogens. 2009;5:e1000629.
105. Kepp O, Rajalingam K, Kimmig S, Rudel T. BAK and BAX are non-redundant during infection- and DNA damage-induced apoptosis. EMBO J. 2007;26:825–834.
106. Kepp O, Gottschalk K, Churin Y, et al. Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection. PLoS Pathogens. 2009;5:e1000348.
107. Terai C, Kornbluth RS, Pauza CD, Richman DD, Carson DA. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest. 1991;87:1710–1715.
108. Doitsh G, Galloway NL, Geng X, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2013;23:509–514.
109. Monroe KM, Yang Z, Johnson JR, et al. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science. 2014;343:428–432.
110. Clarke P, Beckham JD, Leser JS, Hoyt CC, Tyler KL. Fas-mediated apoptotic signaling in the mouse brain following reovirus infection. J Virol. 2009;83:6161–6170.
111. Hughes PD, Belz GT, Fortner KA, Budd RC, Strasser A, Bouillet P. Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity. 2008;28:197–205.
112. O'Donnell JA, Kennedy CL, Pellegrini M, et al. Fas regulates neutrophil lifespan during viral and bacterial infection. J Leukoc Biol. 2015;97:321–326.
113. Croker BA, O'Donnell JA, Nowell CJ, et al. Fas-mediated neutrophil apoptosis is accelerated by Bid, BAK, and BAX and inhibited by Bcl-2 and Mcl-1. Proc Natl Acad Sci USA. 2011;108:13135–13140.
114. Chen W, Calvo PA, Malide D, et al. A novel influenza A virus mitochondrial protein that induces cell death. Nat Med. 2001;7:1306–1312.
115. Jaworska J, Coulombe F, Downey J, et al. NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein. Proc Natl Acad Sci USA. 2014;111:E2110–E2119.
116. Real F, Florentino PT, Reis LC, et al. Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions. Cell Microbiol. 2014;16:1549–1564.
117. Isaac DT, Berkes CA, English BC, et al. Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H. capsulatum infection. Mol Microbiol. 2015;98:910–929.
118. Sebghati TS, Engle JT, Goldman WE. Intracellular parasitism by Histoplasma capsulatum: fungal virulence and calcium dependence. Science. 2000;290:1368–1372.
119. Abu-Zant A, Santic M, Molmeret M, Jones S, Helbig J, Abu Kwaik Y. Incomplete activation of macrophage apoptosis during intracellular replication of Legionella pneumophila. Infect Immun. 2005;73:5339–5349.
120. Zhu W, Hammad LA, Hsu F, Mao Y, Luo ZQ. Induction of caspase 3 activation by multiple L. pneumophila Dot/Icm substrates. Cell Microbiol. 2013;15:1783–1795.
121. Dolezal P, Aili M, Tong J, et al. Legionella pneumophila secretes a mitochondrial carrier protein during infection. PLoS Pathogens. 2012;8:e1002459.
122. Rolando M, Escoll P, Nora T, et al. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. Proc Natl Acad Sci USA. 2016;113:1901–1906.
123. Ren D, Tu HC, Kim H, et al. BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science. 2010;330:1390–1393.
124. Goodall KJ, Finch-Edmondson ML, van Vuuren J, et al. Cycloheximide can induce BAX/BAK dependent myeloid cell death independently of multiple BH3-only proteins. PLoS One. 2016;11:e0164003.
125. Lemaitre B, Girardin SE. Translation inhibition and metabolic stress pathways in the host response to bacterial pathogens. Nat Rev Microbiol. 2013;11:365–369.
126. Fontana MF, Banga S, Barry KC, et al. Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila. PLoS Pathogens. 2011;7:e1001289.
127. Asrat S, Dugan AS, Isberg RR. The frustrated host response to Legionella pneumophila is bypassed by MyD88-dependent translation of pro-inflammatory cytokines. PLoS Pathogens. 2014;10:e1004229.
128. Barry KC, Ingolia NT, Vance RE. Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen. Elife. 2017;6:e22707.
129. Hempstead AD, Isberg RR. Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response. Proc Natl Acad Sci USA. 2015;112:E6790–E6797.
130. Barry KC, Fontana MF, Portman JL, Dugan AS, Vance RE. IL-1alpha signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo. J Immunol. 2013;190:6329–6339.
131. Lin AE, Beasley FC, Keller N, et al. A group A Streptococcus ADP-ribosyltransferase toxin stimulates a protective interleukin 1beta-dependent macrophage immune response. mBio. 2015;6:e00133.
132. Ohmer M, Weber A, Sutter G, Ehrhardt K, Zimmermann A, Hacker G. Anti-apoptotic Bcl-XL but not Mcl-1 contributes to protection against virus-induced apoptosis. Cell Death Dis. 2016;7:e2340.
133. Cummins NW, Sainski-Nguyen AM, Natesampillai S, Aboulnasr F, Kaufmann S, Badley AD. Maintenance of the HIV reservoir is antagonized by selective BCL2 inhibition. J Virol. 2017;91:e00012–e00017.
134. Ebert G, Allison C, Preston S, et al. Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci USA. 2015;112:5803–5808.
135. Ebert G, Preston S, Allison C, et al. Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus. Proc Natl Acad Sci USA. 2015;112:5797–5802.
136. Condon SM, Mitsuuchi Y, Deng Y, et al. Birinapant, a Smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies. J Med Chem. 2014;57:3666–3677.
137. Mason KD, Carpinelli MR, Fletcher JI, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128:1173–1186.
138. Kotschy A, Szlavik Z, Murray J, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016;538:477–482.
139. Tao ZF, Hasvold L, Wang L, et al. Discovery of a potent and selective BCL-XL inhibitor with in vivo activity. ACS Med Chem Lett. 2014;5:1088–1093.