title: Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence.
abstract: Macrophages infected with attenuated Mycobacterium tuberculosis strain H37Ra become apoptotic, which limits bacterial replication and facilitates antigen presentation. Here we demonstrate that cells infected with H37Ra became apoptotic after the formation of an apoptotic envelope on their surface was complete. This process required exposure of phosphatidylserine on the cell surface, followed by deposition of the phospholipid-binding protein annexin-1 and then transglutaminase-mediated crosslinking of annexin-1 through its amino-terminal domain. In macrophages infected with the virulent strain H37Rv, in contrast, the amino-terminal domain of annexin-1 was removed by proteolysis, thus preventing completion of the apoptotic envelope, which resulted in macrophage death by necrosis. Virulent M. tuberculosis therefore avoids the host defense system by blocking formation of the apoptotic envelope, which leads to macrophage necrosis and dissemination of infection in the lung.
authors.affiliation: Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Huixian
authors.initials: H
authors.lastname: Gan
authors.forename: Jinhee
authors.initials: J
authors.lastname: Lee
authors.forename: Fucheng
authors.initials: F
authors.lastname: Ren
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.forename: Hardy
authors.initials: H
authors.lastname: Kornfeld
authors.forename: Heinz G
authors.initials: HG
authors.lastname: Remold
mesh_terms: D000818:Animals; D017302:Annexins / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D009336:Necrosis / Q000276:immunology; D017396:Plasminogen Activator Inhibitor 2 / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000276:immunology*; D014774:Virulence
chemical_list: D017302:Annexins; D008565:Membrane Proteins; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger
references.citation: J Biol Chem. 1991 Jan 15;266(2):1101-8
references.pmid: 1670773
references.citation: Annu Rev Cell Dev Biol. 2004;20:367-94
references.pmid: 15473845
references.citation: J Immunol. 2006 Apr 1;176(7):4267-74
references.pmid: 16547264
references.citation: Infect Immun. 2003 Apr;71(4):1763-73
references.pmid: 12654790
references.citation: Biochem Biophys Res Commun. 1989 Sep 15;163(2):944-51
references.pmid: 2571332
references.citation: Cancer Res. 1990 Jan 1;50(1):120-8
references.pmid: 1967140
references.citation: J Clin Invest. 2001 Oct;108(7):957-62
references.pmid: 11581295
references.citation: Eur J Cell Biol. 1993 Feb;60(1):210-6
references.pmid: 8096461
references.citation: J Hepatol. 2001 Sep;35(3):367-75
references.pmid: 11592598
references.citation: Immunity. 2006 Jan;24(1):105-17
references.pmid: 16413927
references.citation: J Immunol. 2007 Aug 15;179(4):2509-19
references.pmid: 17675513
references.citation: J Clin Invest. 2005 Jun;115(6):1601-6
references.pmid: 15931391
references.citation: J Struct Biol. 2001 Jan;133(1):55-63
references.pmid: 11356064
references.citation: Blood. 1995 Dec 1;86(11):4007-24
references.pmid: 7492756
references.citation: Tuberculosis (Edinb). 2002;82(2-3):55-61
references.pmid: 12356455
references.citation: J Biol Chem. 1986 Aug 25;261(24):11207-13
references.pmid: 3090045
references.citation: J Biol Chem. 1995 Jul 28;270(30):17702-11
references.pmid: 7543090
references.citation: J Immunol. 2003 Jan 1;170(1):430-7
references.pmid: 12496428
references.citation: Cell Death Differ. 1998 Feb;5(2):163-71
references.pmid: 10200461
references.citation: J Exp Med. 1984 Jun 1;159(6):1653-68
references.pmid: 6374011
references.citation: Eur J Biochem. 1993 May 15;214(1):141-6
references.pmid: 8099547
references.citation: J Biol Chem. 1994 May 27;269(21):15394-8
references.pmid: 7910824
references.citation: Nature. 2005 Apr 7;434(7034):767-72
references.pmid: 15815631
references.citation: J Biol Chem. 1992 Apr 5;267(10):7089-94
references.pmid: 1551915
references.citation: Dev Cell. 2003 Apr;4(4):587-98
references.pmid: 12689596
references.citation: J Biol Chem. 1987 May 15;262(14):6931-7
references.pmid: 2952659
references.citation: Am J Pathol. 2001 Feb;158(2):603-15
references.pmid: 11159197
references.citation: J Immunol. 1998 Jun 1;160(11):5448-54
references.pmid: 9605147
references.citation: J Immunol. 2001 Apr 1;166(7):4604-11
references.pmid: 11254718
references.citation: Exp Cell Res. 2000 Apr 10;256(1):42-9
references.pmid: 10739650
references.citation: Science. 2007 Jan 26;315(5811):509-13
references.pmid: 17255510
references.citation: J Leukoc Biol. 1999 Jul;66(1):172-82
references.pmid: 10411006
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: Am J Respir Cell Mol Biol. 2003 Nov;29(5):545-51
references.pmid: 12748057
references.citation: Nat Med. 2003 Aug;9(8):1039-46
references.pmid: 12872166
references.citation: J Infect Dis. 2004 Sep 15;190(6):1167-76
references.pmid: 15319868
references.citation: Cell Death Differ. 2001 Feb;8(2):113-26
references.pmid: 11313713
references.citation: Cell Mol Life Sci. 2004 Feb;61(3):301-25
references.pmid: 14770295
references.citation: J Biol Chem. 1997 May 2;272(18):12035-46
references.pmid: 9115270
references.citation: J Immunol. 1995 Aug 1;155(3):1304-15
references.pmid: 7636197
references.citation: Infect Immun. 1997 Jan;65(1):298-304
references.pmid: 8975927
references.citation: Infect Immun. 2003 Jan;71(1):254-9
references.pmid: 12496173
references.citation: J Immunol. 1997 May 1;158(9):4320-7
references.pmid: 9126994
references.citation: Annu Rev Physiol. 1998;60:619-42
references.pmid: 9558479
references.citation: J Immunol. 2003 Mar 1;170(5):2409-16
references.pmid: 12594264
references.citation: Nat Rev Mol Cell Biol. 2005 Jun;6(6):449-61
references.pmid: 15928709
references.citation: J Immunol. 2006 Mar 15;176(6):3707-16
references.pmid: 16517739
references.citation: J Biol Chem. 1991 Aug 15;266(23):15240-3
references.pmid: 1714455
references.citation: J Leukoc Biol. 2006 Jan;79(1):80-6
references.pmid: 16275894
references.citation: J Cell Sci. 1998 May;111 ( Pt 10):1405-18
references.pmid: 9570758
references.citation: Exp Cell Res. 1995 Mar;217(1):65-71
references.pmid: 7867722
references.citation: Biochemistry. 1978 Jun 27;17(13):2598-604
references.pmid: 28146
references.citation: J Immunol. 2000 Feb 15;164(4):2016-20
references.pmid: 10657653
references.citation: Nat Immunol. 2001 Jul;2(7):612-9
references.pmid: 11429545
references.citation: J Immunol. 2001 Jun 15;166(12):7128-35
references.pmid: 11390458
references.citation: J Biol Chem. 1995 Nov 17;270(46):27894-904
references.pmid: 7499264
references.citation: J Immunol. 1998 Sep 1;161(5):2636-41
references.pmid: 9725266
references.citation: J Biol Chem. 2003 Dec 19;278(51):51613-21
references.pmid: 14532286