Mycobacterium tuberculosis-induced gamma interferon production by natural killer cells requires cross talk with antigen-presenting cells involving Toll-like receptors 2 and 4 and the mannose receptor in tuberculous pleurisy.
Tuberculous pleurisy allows the study of human cells at the site of active Mycobacterium tuberculosis infection. In this study, we found that among pleural fluid (PF) lymphocytes, natural killer (NK) cells are a major source of early gamma interferon (IFN-gamma) upon M. tuberculosis stimulation, leading us to investigate the mechanisms and molecules involved in this process. We show that the whole bacterium is the best inducer of IFN-gamma, although a high-molecular-weight fraction of culture filtrate proteins from M. tuberculosis H37Rv and the whole-cell lysate also induce its expression. The mannose receptor seems to mediate the inhibitory effect of mannosylated lipoarabinomannan, and Toll-like receptor 2 and 4 agonists activate NK cells but do not induce IFN-gamma like M. tuberculosis does. Antigen-presenting cells (APC) and NK cells bind M. tuberculosis, and although interleukin-12 is required, it is not sufficient to induce IFN-gamma expression, indicating that NK cell-APC contact takes place. Indeed, major histocompatibility complex class I, adhesion, and costimulatory molecules as well as NK receptors regulate IFN-gamma induction. The signaling pathway is partially inhibited by dexamethasone and sensitive to Ca2+ flux and cyclosporine. Inhibition of p38 and extracellular-regulated kinase mitogen-activated protein kinase pathways reduces the number of IFN-gamma+ NK cells. Phosphorylated p38 (p-p38) is detected in ex vivo PF-NK cells, and M. tuberculosis triggers p-p38 in PF-NK cells at the same time that binding between NK and M. tuberculosis reaches its maximum value. Thus, interplay between M. tuberculosis and NK cells/APC triggering IFN-gamma would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a type 1 profile.
Schierloh
Pablo
P
Departamento de Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Yokobori
Noemí
N
Alemán
Mercedes
M
Landoni
Verónica
V
Geffner
Laura
L
Musella
Rosa M
RM
Castagnino
Jorge
J
Baldini
Matias
M
Abbate
Eduardo
E
de la Barrera
Silvia S
SS
Sasiain
María C
MC
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D000954:Antigens, Surface / Q000276:immunology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000276:immunology; D045424:Complex Mixtures / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology; D037181:Lectins, C-Type / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010996:Pleural Effusion / Q000276:immunology / Q000382:microbiology; D011956:Receptors, Cell Surface / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000276:immunology* / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000954:Antigens, Surface; D001426:Bacterial Proteins; D045424:Complex Mixtures; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C050016:lipoarabinomannan; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
J Immunol. 2001 Jun 1;166(11):6477-82
11359797
Blood. 2004 Sep 15;104(6):1778-83
15166032
Nat Immunol. 2001 Oct;2(10):947-50
11547333
Proteomics. 2001 Apr;1(4):574-86
11681210
Trends Immunol. 2001 Nov;22(11):633-40
11698225
J Exp Med. 2002 Feb 4;195(3):335-41
11828008
Clin Microbiol Rev. 2002 Apr;15(2):294-309
11932234
J Leukoc Biol. 2002 Aug;72(2):305-11
12149421
J Immunol. 2002 Sep 15;169(6):3155-62
12218133
Scand J Immunol. 2002 Dec;56(6):611-8
12472673
J Exp Med. 2003 Jan 6;197(1):7-17
12515809
J Exp Med. 2003 Jan 6;197(1):121-7
12515819
Cell Microbiol. 2003 Mar;5(3):133-42
12614457
Blood. 2003 Apr 15;101(8):3052-7
12480696
Infect Immun. 2003 Aug;71(8):4238-49
12874299
J Immunol. 2003 Nov 1;171(9):4552-60
14568928
J Immunol. 2003 Nov 15;171(10):5396-405
14607943
Ann Intern Med. 1972 Oct;77(4):507-13
4642731
J Clin Invest. 1994 Apr;93(4):1733-9
7909320
J Exp Med. 1994 Jul 1;180(1):211-22
7516408
Infect Immun. 1995 Apr;63(4):1491-7
7890415
J Clin Invest. 1995 Dec;96(6):2578-82
8675621
Clin Diagn Lab Immunol. 1997 Jan;4(1):49-56
9008280
J Immunol. 1997 Mar 1;158(5):2285-93
9036976
J Immunol. 1998 Jul 1;161(1):400-8
9647249
J Immunol. 2004 Nov 15;173(10):6418-26
15528382
Blood. 2004 Dec 15;104(13):4157-64
15315972
Blood. 2005 Jan 1;105(1):282-8
15345584
Annu Rev Immunol. 2005;23:225-74
15771571
Blood. 2005 Apr 15;105(8):3011-8
15604218
Infect Immun. 2005 Jun;73(6):3547-58
15908384
J Biol Chem. 2005 Jun 3;280(22):20961-7
15809303
J Infect Dis. 2005 Aug 1;192(3):399-409
15995953
J Immunol. 2005 Nov 15;175(10):6852-60
16272343
Immunology. 2005 Dec;116(4):541-52
16313368
Curr Top Microbiol Immunol. 2006;298:1-21
16329183
Curr Top Microbiol Immunol. 2006;298:23-57
16329184
PLoS Med. 2005 Dec;2(12):e381
16279841
Infect Immun. 1999 Nov;67(11):5967-71
10531255
J Exp Med. 2000 Jan 17;191(2):287-302
10637273
J Immunol. 2000 Feb 15;164(4):1768-74
10657623
J Immunol. 2000 Jul 1;165(1):139-47
10861046
J Immunol. 2000 Aug 1;165(3):1307-13
10903731
Infect Immun. 2000 Dec;68(12):6883-90
11083809
J Immunol. 2001 Mar 15;166(6):4074-82
11238656
EMBO Rep. 2000 Nov;1(5):428-34
11258483
Clin Exp Immunol. 2006 Jan;143(1):150-60
16367946
Infect Immun. 2006 May;74(5):2686-96
16622205
J Immunol. 2006 Nov 15;177(10):7086-93
17082625
J Immunol. 2004 Jan 1;172(1):138-43
14688319
J Immunol. 2004 Feb 1;172(3):1455-62
14734722
Microbes Infect. 2004 Aug;6(10):946-59
15310472
Infect Immun. 2004 Sep;72(9):5150-8
15322009
J Immunol. 2001 Jun 15;166(12):7477-85
11390501