Yonsei Med J.  2009 Feb;50(1):1-11. 10.3349/ymj.2009.50.1.1.

Macrophage Apoptosis in Tuberculosis

• Lee J
• Hartman M
• Kornfeld H

• KMID: 1782961
• DOI: http://doi.org/10.3349/ymj.2009.50.1.1

Abstract

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.

Keyword

Tuberculosis; macrophage; apoptosis; mycobacterium; host defense

MeSH Terms

Animals
Apoptosis/*immunology
Humans
Macrophages/*cytology/*microbiology
Mycobacterium tuberculosis/*immunology
Tuberculosis, Pulmonary/*immunology

Reference

1. Schlesinger LS. Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J Immunol. 1993. 150:2920–2930.

2. Zimmerli S, Edwards S, Ernst JD. Selective receptor blockade during phagocytosis does not alter the survival and growth of Mycobacterium tuberculosis in human macrophages. Am J Respir Cell Mol Biol. 1996. 15:760–770.

3. Rohde K, Yates RM, Purdy GE, Russell DG. Mycobacterium tuberculosis and the environment within the phagosome. Immunol Rev. 2007. 219:37–54.

4. Flynn JL, Chan J. Immunology of tuberculosis. Annu Rev Immunol. 2001. 19:93–129.

5. Leemans JC, Juffermans NP, Florquin S, van Rooigen N, Veroordeldonk MJ, Verbon A, et al. Depletion of alveolar macrophages exerts protective effects in pulmonary tuberculosis in mice. J Immunol. 2001. 166:4604–4611.

6. Knapp S, Leemans JC, Florquin S, Branger J, Maris NA, Pater J, et al. Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia. Am J Respir Crit Care Med. 2003. 167:171–179.

7. Canetti G. Present aspects of bacterial resistance in tuberculosis. Am Rev Respir Dis. 1965. 92:687–703.

8. Roulston A, Marcellus RC, Branton PE. Viruses and apoptosis. Annu Rev Microbiol. 1999. 53:577–628.

9. McCormick AL. Control of apoptosis by human cytomegalovirus. Curr Top Microbiol Immunol. 2008. 325:281–295.

10. Clouston WM, Kerr JF. Apoptosis, lymphocytotoxicity and the containment of viral infections. Med Hypotheses. 1985. 18:399–404.

11. Ray CA, Black RA, Kronheim SR, Greenstreet TA, Sleath PR, Salvesen GS, et al. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992. 69:597–604.

12. Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991. 254:1388–1390.

13. Zychlinsky A. Programmed cell death in infectious diseases. Trends Microbiol. 1993. 1:114–117.

14. Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest. 2002. 109:41–50.

15. Chung EY, Kim SJ, Ma XJ. Regulation of cytokine production during phagocytosis of apoptotic cells. Cell Res. 2006. 6:154–161.

16. Schaible UE, Winau F, Sieling PA, Fischer K, Collins HL, Hagens K, et al. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med. 2003. 9:1039–1046.

17. Creagh EM, Conroy H, Martin SJ. Caspase-activation pathways in apoptosis and immunity. Immunol Rev. 2003. 193:10–21.

18. Chen M, Wang J. Initiator caspases in apoptosis signaling pathways. Apoptosis. 2002. 7:313–319.

19. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008. 9:231–241.

20. Riedl SJ, Salvesen GS. The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol. 2007. 8:405–413.

21. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008. 9:47–59.

22. Lockshin RA, Zakeri Z. Caspase-independent cell deaths. Curr Opin Cell Biol. 2002. 14:727–733.

23. Kroemer G, Martin SJ. Caspase-independent cell death. Nat Med. 2005. 11:725–730.

24. Bröker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res. 2005. 11:3155–3162.

25. Guicciardi ME, Leist M, Gores GJ. Lysosomes in cell death. Oncogene. 2004. 23:2881–2890.

26. Chwieralski CE, Welte T, Bühling F. Cathepsin-regulated apoptosis. Apoptosis. 2006. 11:143–149.

27. Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001. 9:113–114.

28. Henry T, Monack DM. Activation of the inflammasome upon Francisella tularensis infection: interplay of innate immune pathways and virulence factors. Cell Microbiol. 2007. 9:2543–2551.

29. Cervantes J, Nagata T, Uchijima M, Shibata K, Koide Y. Intracytosolic Listeria monocytogenes induces cell death through caspase-1 activation in murine macrophages. Cell Microbiol. 2008. 10:41–52.

30. Suzuki T, Franchi L, Toma C, Ashida H, Ogawa M, Yoshikawa Y, et al. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 2007. 3:e111.

31. Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene. 2008. 27:6434–6451.

32. Keane J, Balcewicz-Sablinska MK, Remold HG, Chupp GL, Meek BB, Fenton MJ, et al. Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect Immun. 1997. 65:298–304.

33. Keane J, Remold HG, Kornfeld H. Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol. 2000. 164:2016–2020.

34. Spira A, Carroll JD, Liu G, Aziz Z, Shah V, Kornfeld H, et al. Apoptosis genes in human alveolar macrophages infected with virulent or attenuated Mycobacterium tuberculosis: A pivotal role for tumor necrosis factor. Am J Respir Cell Mol Biol. 2003. 29:545–551.

35. 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.

36. 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.

37. Molloy A, Laochumroonvorapong P, Kaplan G. Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guérin. J Exp Med. 1994. 180:1499–1509.

38. Riendeau CJ, Kornfeld H. THP-1 cell apoptosis in response to Mycobacterial infection. Infect Immun. 2003. 71:254–259.

39. Oddo M, Renno T, Attinger A, Bakker T, MacDonald HR, Meylan PR. Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis. J Immunol. 1998. 160:5448–5454.

40. Velmurugan K, Chen B, Miller JL, Azogue S, Gurses S, Hsu T, et al. Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog. 2007. 3:e110.

41. Fratazzi C, Arbeit RD, Carini C, Remold HG. Programmed cell death of Mycobacterium avium serovar 4-infected human macrophages prevents mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages. J Immunol. 1997. 158:4320–4327.

42. Lee J, Remold HG, Ieong MH, Kornfeld H. Macrophage apoptosis in response to high intracellular burden of Mycobacterium tuberculosis is mediated by a novel caspase-independent pathway. J Immunol. 2006. 176:4267–4274.

43. Hinchey J, Lee S, Jeon BY, Basaraba RJ, Venkataswamy MM, Chen B, et al. Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Invest. 2007. 117:2279–2288.

44. Park JS, Tamayo MH, Gonzalez-Juarrero M, Orme IM, Ordway DJ. Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages. J Leukoc Biol. 2006. 79:80–86.

45. Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 2005. 12 Suppl 2:1463–1467.

46. Teitelbaum R, Cammer M, Maitland ML, Freitag NE, Condeelis J, Bloom BR. Mycobacterial infection of macrophages results in membrane-permeable phagosomes. Proc Natl Acad Sci U S A. 1999. 96:15190–15195.

47. van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J, et al. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. 2007. 129:1287–1298.

48. Bursch W. The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ. 2001. 8:569–581.

49. Rojas M, Barrera LF, Puzo G, Garcia LF. Differential induction of apoptosis by virulent Mycobacterium tuberculosis in resistant and susceptible murine macrophages: role of nitric oxide and mycobacterial products. J Immunol. 1997. 159:1352–1361.

50. Rojas M, Barrera LF, García LF. Induction of apoptosis in murine macrophages by Mycobacterium tuberculosis is reactive oxygen intermediates-independent. Biochem Biophys Res Commun. 1998. 247:436–442.

51. Rojas M, Olivier M, Gros P, Barrera LF, García LF. TNF-alpha and IL-10 modulate the induction of apoptosis by virulent Mycobacterium tuberculosis in murine macrophages. J Immunol. 1999. 162:6122–6131.

52. Ciaramella A, Cavone A, Santucci MB, Garg SK, Sanarico N, Bocchino M, et al. Induction of apoptosis and release of interleukin-1 beta by cell wall-associated 19-kDa lipoprotein during the course of mycobacterial infection. J Infect Dis. 2004. 190:1167–1176.

53. López M, Sly LM, Luu Y, Young D, Cooper H, Reiner NE. The 19-kDa Mycobacterium tuberculosis protein induces macrophage apoptosis through Toll-like receptor-2. J Immunol. 2003. 170:2409–2416.

54. Smith RA, Alvarez AJ, Estes DM. The P2X7 purinergic receptor on bovine macrophages mediates mycobacterial death. Vet Immunol Immunopathol. 2001. 78:249–262.

55. Fairbairn IP, Stober CB, Kumararatne DS, Lammas DA. ATP-mediated killing of intracellular mycobacteria by bacterial death by phagosome-lysosome fusion. J Immunol. 2001. 167:3300–3307.

56. Biswas D, Qureshi OS, Lee WY, Croudace JE, Mura M, Lammas DA. ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages. BMC Immunol. 2008. 9:35.

57. Pan H, Yan BS, Rojas M, Shebzukhov YV, Zhou H, Kobzik L, et al. Ipr1 gene mediates innate immunity to tuberculosis. Nature. 2005. 434:767–772.

58. Gan H, Lee J, Ren F, Chen M, Kornfeld H, Remold HG. Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence. Nat Immunol. 2008. 9:1189–1197.

59. Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol. 2008. 9:1179–1188.

60. Turner OC, Basaraba RJ, Orme IM. Immunopathogenesis of pulmonary granulomas in the guinea pig after infection with Mycobacterium tuberculosis. Infect Immun. 2003. 71:864–871.

61. Gil O, Guirado E, Gordillo S, Díaz J, Tapia G, Vilaplana C, et al. Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type. Microbes Infect. 2006. 8:628–636.

62. Pandey AK, Sassetti CM. Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci U S A. 2008. 105:4376–4380.

63. Wong H, Hashimoto S. Accumulation of cholesteryl ester and lipid droplets in macrophages after uptake of cholesterol-rich necrotic products. Arteriosclerosis. 1987. 7:185–190.

64. Placido R, Mancino G, Amendola A, Mariani F, Vendetti S, Piacentini M, et al. Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection. J Pathol. 1997. 181:31–38.

65. Sánchez MD, García Y, Montes C, París SC, Rojas M, Barrera LF, et al. Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment. Microbes Infect. 2006. 8:2492–2500.

66. Murphy FJ, Seery LT, Hayes I. Therapeutic approaches to the modulation of apoptosis. Essays Biochem. 2003. 39:131–153.

67. Reed JC. Apoptosis mechanisms: implications for cancer drug discovery. Oncology (Williston Park). 2004. 18:13 Suppl 10. 11–20.

68. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001. 345:1098–1104.

69. Condos R, Rom WN, Schluger NW. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-gamma via aerosol. Lancet. 1997. 349:1513–1515.

70. Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser-Eddine A, et al. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest. 2005. 115:2472–2479.