Insights into battles between Mycobacterium tuberculosis and macrophages

Abstract

As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years. The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses. The signaling pathways that involve TNF, typeI IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes.

Keywords

Mycobacterium tuberculosis / macrophages / necroptosis / apoptosis / autophagy / tumor necrosis factor (TNF) / type I Interferons (IFNs)

References

[1] Abdallah AM, Bestebroer J, Savage NDL, de Punder K, van Zon M, Wilson L, Korbee CJ, van der Sar AM, Ottenhoff THM, van der Wel NN (2011) Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation. J Immunol187: 4744-4753

[2] Andersen P (1997) Host responses and antigens involved in protective immunity to Mycobacterium tuberculosis. Scand J Immunol45: 115-131

[3] Balcewicz-Sablinska MK, Keane J, Kornfeld H, Remold HG (1998) Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha. J Immunol161: 2636-2641

[4] Behar SM, Divangahi M, Remold HG (2010) Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? Nat Rev Microbiol8: 668-674

[5] Behar SM, Martin CJ, Booty MG, Nishimura T, Zhao X, Gan H, Divangahi M, Remold HG (2011) Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunol4: 279-287

[6] Bhatt K, Salgame P (2007) Host innate immune response to Mycobacterium tuberculosis. J Clin Immunol27: 347-362

[7] Bogdan C (2000) The function of type I interferons in antimicrobial immunity. Curr Opin Immunol12: 419-424

[8] Bordón J, Plankey MW, Young M, Greenblatt RM, Villacres MC, French AL, Zhang J, Brock G, Appana S, Herold B, Durkin H, Golub JE, Fernandez-Botran R (2011) Lower levels of interleukin-12 precede the development of tuberculosis among HIV-infected women. Cytokine56: 325-331

[9] Bouchonnet F, Boechat N, Bonay M, Hance AJ (2002) Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG. Infect Immun70: 3020-3025

[10] Bradfute SB, Castillo EF, Arko-Mensah J, Chauhan S, Jiang S, Mandell M, Deretic V (2013) Autophagy as an immune effector against tuberculosis. Curr Opin Microbiol16: 355-365

[11] Brune B (2003) Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ10: 864-869

[12] Chawla-Sarkar M, Lindner DJ, Liu YF, Williams BR, Sen GC, Silverman RH, Borden EC (2003) Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis8: 237-249

[13] Chen Q, Gong B, Mahmoud-Ahmed AS, Zhou A, Hsi ED, Hussein M, Almasan A (2001) Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Blood98: 2183-2192

[14] Desvignes L, Wolf AJ, Ernst JD (2012) Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis. J Immunol188: 6205-6215

[15] Dondelinger Y, Aguileta MA, Goossens V, Dubuisson C, Grootjans S, Dejardin E, Vandenabeele P, Bertrand MJM (2013) RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ20: 1381-1392

[16] Du QL, Xie JP, Kim HJ, Ma XJ (2013) Type I interferon: the mediator of bacterial infection-induced necroptosis. Cell Mol Immunol10: 4-6

[17] Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, Lee HM, Krutzik SR, Schenk M, Sieling PA, Teles R, Montoya D, Iyer SS, Bruns H, Lewinsohn DM, Hollis BW, Hewison M, Hewison M, Adams JS, Steinmeyer A, Steinmeyer A, Zügel U, Cheng G, Jo EK, Bloom BR, Modlin RL (2011) Vitamin D is required for IFNgamma- mediated antimicrobial activity of human macrophages. Sci Transl Med3: 104ra102

[18] Flynn JL, Chan J (2001) Immunology of tuberculosis. Ann Rev Immunol19: 93-129

[19] Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell147: 742-758

[20] Galluzzi L, Kroemer G (2008) Necroptosis: a specialized pathway of programmed necrosis. Cell135: 1161-1163

[21] Gonzalez-Navajas JM, Lee J, David M, Raz E (2012) Immunomodulatory functions of type I interferons. Nat Rev Immunol12: 125-135

[22] Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Förster I, Farlik M, Decker T, Du Pasquier RA, Romero P, Tschopp J (2011) Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity34: 213-223

[23] Guirado E, Schlesinger LS, Kaplan G (2013) Macrophages in tuberculosis: friend or foe. Semin Immunopathol35: 563-583

[24] Han JH, Zhong CQ, Zhang DW (2011) Programmed necrosis: backup to and competitor with apoptosis in the immune system. Nat Immunol12: 1143-1149

[25] Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature410: 1099-1103

[26] Hinchey J, Lee S, Jeon BY, Basaraba RJ, Venkataswamy MM, Chen B, Chan J, Braunstein M, Orme IM, Derrick SC (2007) Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Investig117: 2279-2288

[27] Jayachandran R, BoseDasgupta S, Pieters J (2013) Surviving the macrophage: tools and tricks employed by Mycobacterium tuberculosis. Curr Top Microbiol Immunol374: 189-209

[28] Jayakumar D, Jacobs WR, Narayanan S (2008) Protein kinase E of Mycobacterium tuberculosis has a role in the nitric oxide stress response and apoptosis in a human macrophage model of infection. Cell Microbiol10: 365-374

[29] Jayaraman P, Sada-Ovalle I, Nishimura T, Anderson AC, Kuchroo VK, Remold HG, Behar SM (2013) IL-1 beta promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. J Immunol190: 4196-4204

[30] Jiang WW, Bell CW, Pisetsky DS (2007) The relationship between apoptosis and high-mobility group protein 1 release from murine macrophages stimulated with lipopolysaccharide or polyinosinicpolycytidylic acid. J Immunol178: 6495-6503

[31] Keane J, Remold HG, Kornfeld H (2000) Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol164: 2016-2020

[32] Killick KE, Cheallaigh CN, O’Farrelly C, Hokamp K, MacHugh DE, Harris J (2013) Receptor-mediated recognition of mycobacterial pathogens. Cell Microbiol15: 1484-1495

[33] Kumar D, Nath L, Kamal MA, Varshney A, Jain A, Singh S, Rao KVS (2010) Genome-wide analysis of the host intracellular network that regulates survival of Mycobacteriumtuberculosis. Cell140: 731-743

[34] Kundu M, Pathak SK, Kumawat K, Basu S, Chatterjee G, Pathak S, Noguchi T, Takeda K, Ichijo H, Thien CBF (2009) A TNF- and c-Cbl-dependent FLIPS-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis. Nat Immunol10: 918-926

[35] Liang SJ, Qin XB (2013) Critical role of type I interferon-induced macrophage necroptosis during infection with Salmonella enterica serovar typhimurium. Cell Mol Immunol10: 99-100

[36] Liu PT, Stenger S, Li HY, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C (2006) Toll-like receptor riggering of a vitamin D-mediated human antimicrobial response. Science311: 1770-1773

[37] Mata-Granados JM, Cuenca-Acebedo R, de Castro MDL, Gomez JMQ (2013) Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study. J Bone Miner Metab31: 455-460

[38] Miller JL, Velmurugan K, Cowan MJ, Briken V (2010) The type I NADH dehydrogenase of Mycobacterium tuberculosis counters phagosomal NOX2 activity to inhibit TNF-alpha-mediated host cell apoptosis. Plos Pathog6: e1000864

[39] Mouli VP, Ananthakrishnan AN (2014) Review article: vitamin D and inflammatory bowel diseases. Alimentary Pharmacol Ther39: 125-136

[40] Novikov A, Cardone M, Thompson R, Shenderov K, Kirschman KD, Mayer-Barber KD, Myers TG, Rabin RL, Trinchieri G, Sher A (2011) Mycobacterium tuberculosis triggers host type I IFN signaling to regulate IL-1 beta production in human macrophages. J Immunol187: 2540-2547

[41] Nursyam EW, Amin Z, Rumende CM (2006) The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones38: 3-5

[42] Prabhakar S, Qiao YM, Hoshino Y, Weiden M, Canova A, Giacomini E, Coccia E, Pine R (2003) Inhibition of response to alpha interferon by Mycobacterium tuberculosis. Infect Immun71: 2487-2497

[43] Rakotosamimanana N, Doherty TM, Andriamihantasoa LH, Richard V, Gicquel B, Soares JL, Zumla A, Razanamparany VR (2013) Expression of TNF-alpha-dependent apoptosis-related genes in the peripheral blood of malagasy subjects with tuberculosis. Plos One8: 61154

[44] Remijsen Q, Goossens V, Grootjans S, Van den Haute C, Vanlangenakker N, Dondelinger Y, Roelandt R, Bruggeman I, Goncalves A, Bertrand MJM, Baekelandt V, Takahashi N, Berghe TV, Vandenabeele P (2014) Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis. Cell Death Dis5: e1004

[45] Rivas-Santiago B, Hernandez-Pando R, Carranza C, Juarez E, Contreras JL, Aguilar-Leon D, Torres M, Sada E (2008) Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infect Immun76: 935-941

[46] Roca FJ, Ramakrishnan L (2013) TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell153: 521-534

[47] Rockett KA, Brookes R, Udalova I, Vidal V, Hill AVS, Kwiatkowski D (1998) 1,25-dihydroxyvitamin D-3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun66: 5314-5321

[48] Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo SQ, Underwood BR (2011) Complex inhibitory effects of nitric oxide on autophagy. Mol Cell43: 19-32

[49] Schaible UE, Winau F, Sieling PA, Fischer K, Collins HL, Hagens K, Modlin RL, Brinkmann V, Kaufmann SHE (2003) Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med9: 1039-1046

[50] Shin DM, Yuk JM, Lee HM, Lee SH, Son JW, Harding CV, Kim JM, Modlin RL, Jo EK (2010) Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell Microbiol12: 1648-1665

[51] Simmons DP, Canaday DH, Liu Y, Li Q, Huang A, Boom WH, Harding CV (2010) Mycobacterium tuberculosis and TLR2 agonists inhibit induction of type I IFN and class I MHC antigen cross processing by TLR9. J Immunol185: 2405-2415

[52] Sly LM, Hingley-Wilson SM, Reiner NE, McMaster WR (2003) Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1. J Immunol170: 430-437

[53] Songane M, Kleinnijenhuis J, Netea MG, van Crevel R (2012) The role of autophagy in host defence against Mycobacterium tuberculosis infection. Tuberculosis92: 388-396

[54] Underhill DM, Ozinsky A, Smith KD, Aderem A (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory<?Pub Caret?> signaling in macrophages. Proc Natl Acad Sci USA96: 14459-14463

[55] van Heijst JWJ, Pamer EG (2013) Radical host-specific therapies for TB. Cell153: 507-508

[56] van Zoelen MA, Yang H, Florquin S, Meijers JC, Akira S, Arnold B, Nawroth PP, Bierhaus A, Tracey KJ, van der Poll T (2009) Role of toll-like receptors 2 and 4, and the receptor for advanced glycation end products in high-mobility group box 1-induced inflammation in vivo. Shock31: 280-284

[57] Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T (2010) The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal3: re4

[58] Velmurugan K, Chen B, Miller JL, Azogue S, Gurses S, Hsu T, Glickman M, Jacobs WR, Porcelli SA, Briken V (2007) Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. Plos Pathog3: 972-980

[59] Verway M, Bouttier M, Wang TT, Carrier M, Calderon M, An BS, Devemy E, McIntosh F, Divangahi M, Behr MA (2013) Vitamin D induces interleukin-1 beta expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection. Plos Pathog9: e1003407

[60] Veyrier F, Pletzer D, Turenne C, Behr MA (2009) Phylogenetic detection of horizontal gene transfer during the step-wise genesis of Mycobacterium tuberculosis. BMC Evol Biol9: 196

[61] Wang ZG, Jiang H, Chen S, Du FH, Wang XD (2012) The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell148: 228-243

[62] Warner DF, Mizrahi V (2013) Complex genetics of drug resistance in Mycobacterium tuberculosis. Nat Genet45: 1107-1108

[63] WHO (2013) Global tuberculosis report 2013

[64] Wu SP, Sun J (2011) Vitamin D, vitamin D receptor, and macroautophagy in inflammation and infection. Discov Med59: 325-335

[65] Wu ZK, Wang Y, Chen LN (2013) Network-based drug repositioning. Mol Biosyst9: 1268-1281

[66] Yu XW, Li CM, Hong WL, Pan WH, Xie JP (2013) Autophagy during Mycobacterium tuberculosis infection and implications for future tuberculosis medications. Cell Signal25: 1272-1278

[67] Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH, Kim JM, Jo EK (2009) Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe6: 231-243

[68] Zhang Y, Leung DY, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E (2012) Vitamin Dinhibits monocyte/macrophage proinflammatory cytokine production by targeting mitogen-activated protein kinase phosphatase-1. J Allergy Clin Immunol129: Ab146

RIGHTS & PERMISSIONS

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.