Targeting of Heparin-Binding Hemagglutinin to Mitochondria in Macrophages
Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a virulence factor involved in extrapulmonary dissemination and a strong diagnostic antigen against tuberculosis, is both surface-associated and secreted. The role of HBHA in macrophages during M. tuberculosis infection, however, is less well known. Here, we show that recombinant HBHA produced by Mycobacterium smegmatis effectively induces apoptosis in murine macrophages. DNA fragmentation, nuclear condensation, caspase activation, and poly (ADP-ribose) polymerase cleavage were observed in apoptotic macrophages treated with HBHA. Enhanced reactive oxygen species (ROS) production and Bax activation were essential for HBHA-induced apoptosis, as evidenced by a restoration of the viability of macrophages pretreated with N-acetylcysteine, a potent ROS scavenger, or transfected with Bax siRNA. HBHA is targeted to the mitochondrial compartment of HBHA-treated and M. tuberculosis-infected macrophages. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in both macrophages and isolated mitochondria treated with HBHA. Disruption of HBHA gene led to the restoration of ΔΨm impairment in infected macrophages, resulting in reduced apoptosis. Taken together, our data suggest that HBHA may act as a strong pathogenic factor to cause apoptosis of professional phagocytes infected with M. tuberculosis.
Vyšlo v časopise:
Targeting of Heparin-Binding Hemagglutinin to Mitochondria in Macrophages. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002435
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002435
Souhrn
Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a virulence factor involved in extrapulmonary dissemination and a strong diagnostic antigen against tuberculosis, is both surface-associated and secreted. The role of HBHA in macrophages during M. tuberculosis infection, however, is less well known. Here, we show that recombinant HBHA produced by Mycobacterium smegmatis effectively induces apoptosis in murine macrophages. DNA fragmentation, nuclear condensation, caspase activation, and poly (ADP-ribose) polymerase cleavage were observed in apoptotic macrophages treated with HBHA. Enhanced reactive oxygen species (ROS) production and Bax activation were essential for HBHA-induced apoptosis, as evidenced by a restoration of the viability of macrophages pretreated with N-acetylcysteine, a potent ROS scavenger, or transfected with Bax siRNA. HBHA is targeted to the mitochondrial compartment of HBHA-treated and M. tuberculosis-infected macrophages. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in both macrophages and isolated mitochondria treated with HBHA. Disruption of HBHA gene led to the restoration of ΔΨm impairment in infected macrophages, resulting in reduced apoptosis. Taken together, our data suggest that HBHA may act as a strong pathogenic factor to cause apoptosis of professional phagocytes infected with M. tuberculosis.
Zdroje
1. DyeCScheeleSDolinPPathaniaVRaviglioneMC 1999 Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 282 677 686
2. Hingley-WilsonSMSambandamurthyVKJacobsWRJr 2003 Survival perspectives from the world's most successful pathogen, Mycobacterium tuberculosis. Nat Immunol 4 949 955
3. MolloyALaochumroonvorapongPKaplanG 1994 Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guerin. J Exp Med 180 1499 1509
4. TschoppJThomeMHofmannKMeinlE 1998 The fight of viruses against apoptosis. Curr Opin Genet Dev 8 82 87
5. GaoLYKwaikYA 2000 The modulation of host cell apoptosis by intracellular bacterial pathogens. Trends Microbiol 8 306 313
6. KeaneJRemoldHGKornfeldH 2000 Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol 164 2016 2020
7. RiendeauCJKornfeldH 2003 THP-1 cell apoptosis in response to Mycobacterial infection. Infect Immun 71 254 259
8. DhimanRRajeMMajumdarS 2007 Differential expression of NF-kappaB in mycobacteria infected THP-1 affects apoptosis. Biochim Biophys Acta 1770 649 658
9. ZhangJJiangRTakayamaHTanakaY 2005 Survival of virulent Mycobacterium tuberculosis involves preventing apoptosis induced by Bcl-2 upregulation and release resulting from necrosis in J774 macrophages. Microbiol Immunol 49 845 852
10. PlacidoRMancinoGAmendolaAMarianiFVendettiS 1997 Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection. J Pathol 181 31 38
11. KlinglerKTchou-WongKMBrandliOAstonCKimR 1997 Effects of mycobacteria on regulation of apoptosis in mononuclear phagocytes. Infect Immun 65 5272 5278
12. KeaneJBalcewicz-SablinskaMKRemoldHGChuppGLMeekBB 1997 Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect Immun 65 298 304
13. FayyaziAEichmeyerBSoruriASchweyerSHermsJ 2000 Apoptosis of macrophages and T cells in tuberculosis associated caseous necrosis. J Pathol 191 417 425
14. LopezMSlyLMLuuYYoungDCooperH 2003 The 19-kDa Mycobacterium tuberculosis protein induces macrophage apoptosis through Toll-like receptor-2. J Immunol 170 2409 2416
15. BasuSPathakSKBanerjeeAPathakSBhattacharyyaA 2007 Execution of macrophage apoptosis by PE_PGRS33 of Mycobacterium tuberculosis is mediated by Toll-like receptor 2-dependent release of tumor necrosis factor-alpha. J Biol Chem 282 1039 1050
16. DerrickSCMorrisSL 2007 The ESAT6 protein of Mycobacterium tuberculosis induces apoptosis of macrophages by activating caspase expression. Cell Microbiol 9 1547 1555
17. SanchezAEspinosaPEsparzaMAColonMBernalG 2009 Mycobacterium tuberculosis 38-kDa lipoprotein is apoptogenic for human monocyte-derived macrophages. Scand J Immunol 69 20 28
18. MenozziFDRouseJHAlaviMLaude-SharpMMullerJ 1996 Identification of a heparin-binding hemagglutinin present in mycobacteria. J Exp Med 184 993 1001
19. PetheKAlonsoSBietFDeloguGBrennanMJ 2001 The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature 412 190 194
20. ParraMPickettTDeloguGDheenadhayalanVDebrieAS 2004 The mycobacterial heparin-binding hemagglutinin is a protective antigen in the mouse aerosol challenge model of tuberculosis. Infect Immun 72 6799 6805
21. HougardyJMSchepersKPlaceSDrowartALechevinV 2007 Heparin-binding-hemagglutinin-induced IFN-gamma release as a diagnostic tool for latent tuberculosis. PLoS One 2 e926
22. ShinARLeeKSLeeJSKimSYSongCH 2006 Mycobacterium tuberculosis HBHA protein reacts strongly with the serum immunoglobulin M of tuberculosis patients. Clin Vaccine Immunol 13 869 875
23. WikerHGHarboeM 1992 The antigen 85 complex: a major secretion product of Mycobacterium tuberculosis. Microbiol Rev 56 648 661
24. LimJHParkJKJoEKSongCHMinD 1999 Purification and immunoreactivity of three components from the 30/32-kilodalton antigen 85 complex in Mycobacterium tuberculosis. Infect Immun 67 6187 6190
25. KroemerG 1999 Mitochondrial control of apoptosis: an overview. Biochem Soc Symp 66 1 15
26. GreenDRReedJC 1998 Mitochondria and apoptosis. Science 281 1309 1312
27. ElmoreS 2007 Apoptosis: a review of programmed cell death. Toxicol Pathol 35 495 516
28. CorySAdamsJM 2002 The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2 647 656
29. KroemerGZamzamiNSusinSA 1997 Mitochondrial control of apoptosis. Immunol Today 18 44 51
30. BoyaPRoquesBKroemerG 2001 New EMBO members' review: viral and bacterial proteins regulating apoptosis at the mitochondrial level. EMBO J 20 4325 4331
31. RojasMOlivierMGrosPBarreraLFGarciaLF 1999 TNF-alpha and IL-10 modulate the induction of apoptosis by virulent Mycobacterium tuberculosis in murine macrophages. J Immunol 162 6122 6131
32. SantucciMBAmicosanteMCicconiRMontesanoCCasariniM 2000 Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages: early membrane modifications and intracellular mycobacterial viability. J Infect Dis 181 1506 1509
33. Mueller-OrtizSLWangerARNorrisSJ 2001 Mycobacterial protein HbhA binds human complement component C3. Infect Immun 69 7501 7511
34. SchlesingerLSBellinger-KawaharaCGPayneNRHorwitzMA 1990 Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol 144 2771 2780
35. MullerARudelT 2001 Modification of host cell apoptosis by viral and bacterial pathogens. Int J Med Microbiol 291 197 207
36. DuanLGanHGolanDERemoldHG 2002 Critical role of mitochondrial damage in determining outcome of macrophage infection with Mycobacterium tuberculosis. J Immunol 169 5181 5187
37. AdamsJMCoryS 1998 The Bcl-2 protein family: arbiters of cell survival. Science 281 1322 1326
38. GuptaSYelLKimDKimCChiplunkarS 2003 Arsenic trioxide induces apoptosis in peripheral blood T lymphocyte subsets by inducing oxidative stress: a role of Bcl-2. Mol Cancer Ther 2 711 719
39. FiersWBeyaertRDeclercqWVandenabeeleP 1999 More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene 18 7719 7730
40. MassariPHoYWetzlerLM 2000 Neisseria meningitidis porin PorB interacts with mitochondria and protects cells from apoptosis. Proc Natl Acad Sci U S A 97 9070 9075
41. RahmaniZHuhKWLasherRSiddiquiA 2000 Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential. J Virol 74 2840 2846
42. YangJLiuXBhallaKKimCNIbradoAM 1997 Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275 1129 1132
43. KroemerG 1997 The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 3 614 620
44. PetheKBifaniPDrobecqHSergheraertCDebrieAS 2002 Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc Natl Acad Sci U S A 99 10759 10764
45. EllerbyHMArapWEllerbyLMKainRAndrusiakR 1999 Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5 1032 1038
46. ChenMGanHRemoldHG 2006 A mechanism of virulence: virulent Mycobacterium tuberculosis strain H37Rv, but not attenuated H37Ra, causes significant mitochondrial inner membrane disruption in macrophages leading to necrosis. J Immunol 176 3707 3716
47. DivangahiMChenMGanHDesjardinsDHickmanTT 2009 Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair. Nat Immunol 10 899 906
48. ChenMDivangahiMGanHShinDSHongS 2008 Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J Exp Med 205 2791 2801
49. LeeJRemoldHGIeongMHKornfeldH 2006 Macrophage apoptosis in response to high intracellular burden of Mycobacterium tuberculosis is mediated by a novel caspase-independent pathway. J Immunol 176 4267 4274
50. O'SullivanMPO'LearySKellyDMKeaneJ 2007 A caspase-independent pathway mediates macrophage cell death in response to Mycobacterium tuberculosis infection. Infect Immun 75 1984 1993
51. VelmuruganKChenBMillerJLAzogueSGursesS 2007 Mycobacterium tuberculosis nuoG is a virulence gene that inhibits apoptosis of infected host cells. PLoS Pathog 3 e110
52. HincheyJLeeSJeonBYBasarabaRJVenkataswamyMM 2007 Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Invest 117 2279 2288
53. JayakumarDJacobsWRJrNarayananS 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 Microbiol 10 365 374
54. DanelishviliLMcGarveyJLiYJBermudezLE 2003 Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells. Cell Microbiol 5 649 660
55. ChaussabelDSemnaniRTMcDowellMASacksDSherA 2003 Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites. Blood 102 672 681
56. WaterhouseNJGoldsteinJCvon AhsenOSchulerMNewmeyerDD 2001 Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process. J Cell Biol 153 319 328
57. FrezzaCCipolatSScorranoL 2007 Organelle isolation: functional mitochondria from mouse liver, muscle and cultured fibroblasts. Nat Protoc 2 287 295
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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