title: Prominent role for T cell-derived tumour necrosis factor for sustained control of Mycobacterium tuberculosis infection.
abstract: Tumour Necrosis Factor (TNF) is critical for host control of M. tuberculosis, but the relative contribution of TNF from innate and adaptive immune responses during tuberculosis infection is unclear. Myeloid versus T-cell-derived TNF function in tuberculosis was investigated using cell type-specific TNF deletion. Mice deficient for TNF expression in macrophages/neutrophils displayed early, transient susceptibility to M. tuberculosis but recruited activated, TNF-producing CD4(+) and CD8(+) T-cells and controlled chronic infection. Strikingly, deficient TNF expression in T-cells resulted in early control but susceptibility and eventual mortality during chronic infection with increased pulmonary pathology. TNF inactivation in both myeloid and T-cells rendered mice critically susceptible to infection with a phenotype resembling complete TNF deficient mice, indicating that myeloid and T-cells are the primary TNF sources collaborating for host control of tuberculosis. Thus, while TNF from myeloid cells mediates early immune function, T-cell derived TNF is essential to sustain protection during chronic tuberculosis infection.
authors: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors: Nasiema
authors: N
authors: Allie
authors: Sergei I
authors: SI
authors: Grivennikov
authors: Roanne
authors: R
authors: Keeton
authors: Nai-Jen
authors: NJ
authors: Hsu
authors: Marie-Laure
authors: ML
authors: Bourigault
authors: Nathalie
authors: N
authors: Court
authors: Cecile
authors: C
authors: Fremond
authors: Vladimir
authors: V
authors: Yeremeev
authors: Yuriy
authors: Y
authors: Shebzukhov
authors: Bernhard
authors: B
authors: Ryffel
authors: Sergei A
authors: SA
authors: Nedospasov
authors: Valerie F J
authors: VF
authors: Quesniaux
authors: Muazzam
authors: M
authors: Jacobs
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D019426:Integrases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C045073:Cre recombinase; D019426:Integrases
references: Curr Opin Immunol. 2009 Aug;21(4):378-84
references: 19646851
references: Infect Immun. 1997 Dec;65(12):5149-56
references: 9393809
references: Springer Semin Immunopathol. 1988;10(4):337-58
references: 3146818
references: Infect Immun. 1999 Jul;67(7):3242-7
references: 10377097
references: Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):193-209
references: 12787559
references: J Immunol. 1987 Jun 15;138(12):4408-13
references: 3108389
references: Clin Exp Immunol. 1989 May;76(2):240-5
references: 2503277
references: Annu Rev Immunol. 2004;22:599-623
references: 15032590
references: J Clin Invest. 2004 Dec;114(12):1790-9
references: 15599404
references: Infect Immun. 1990 Aug;58(8):2675-7
references: 2115027
references: J Immunol. 1999 Mar 15;162(6):3504-11
references: 10092807
references: Nature. 1997 Feb 20;385(6618):729-33
references: 9034190
references: Am J Pathol. 1993 Jun;142(6):1739-49
references: 7685152
references: Cell Immunol. 1999 May 25;194(1):12-20
references: 10357876
references: Cell. 1989 Mar 10;56(5):731-40
references: 2647299
references: Annu Rev Cell Biol. 1993;9:317-43
references: 8280464
references: Infect Immun. 2007 Apr;75(4):1870-7
references: 17283104
references: Immunity. 1995 Jun;2(6):561-72
references: 7540941
references: Cell Microbiol. 2006 Feb;8(2):218-32
references: 16441433
references: Nature. 1997 Feb 20;385(6618):733-6
references: 9034191
references: Infect Immun. 2000 Dec;68(12):6954-61
references: 11083819
references: J Immunol. 1993 Mar 1;150(5):1886-96
references: 8436823
references: Lab Invest. 2000 Jun;80(6):901-14
references: 10879741
references: FEMS Immunol Med Microbiol. 1994 Mar;8(3):225-32
references: 8004059
references: Curr Opin Immunol. 1995 Aug;7(4):512-6
references: 7495515
references: J Exp Med. 1995 May 1;181(5):1615-21
references: 7722441
references: Int J Immunopharmacol. 1990;12(7):721-7
references: 2127260
references: Eur Cytokine Netw. 1999 Dec;10(4):533-40
references: 10586120
references: Infect Immun. 2000 Feb;68(2):621-9
references: 10639425
references: J Immunol. 1998 May 1;160(9):4490-9
references: 9574555
references: J Immunol. 2010 Oct 1;185(7):4292-301
references: 20817877
references: Immunology. 2008 Dec;125(4):522-34
references: 18544042
references: Annu Rev Immunol. 1992;10:411-52
references: 1590993
references: Immunity. 2005 Jan;22(1):93-104
references: 15664162
references: J Immunol. 1994 Jan 15;152(2):743-53
references: 8283049
references: Eur J Immunol. 2007 Mar;37(3):768-79
references: 17301950
references: J Immunol. 2002 May 1;168(9):4620-7
references: 11971010
references: J Exp Med. 1993 Dec 1;178(6):2249-54
references: 7504064
references: J Immunol. 2001 Aug 15;167(4):2004-10
references: 11489982
references: PLoS One. 2011 Jan 13;6(1):e16161
references: 21249199
references: J Exp Med. 1993 Dec 1;178(6):2243-7
references: 8245795
references: Infect Immun. 1993 Jan;61(1):197-203
references: 8418042
references: Infect Immun. 2004 Mar;72(3):1804-6
references: 14977991
references: J Immunol. 1993 Jul 1;151(1):518-25
references: 8100846
references: J Immunol. 2007 Jul 15;179(2):1178-89
references: 17617611
references: Respir Res. 2005 Nov 14;6:136
references: 16285886
references: J Leukoc Biol. 1992 Mar;51(3):251-5
references: 1541908
references: N Engl J Med. 2001 Oct 11;345(15):1098-104
references: 11596589
references: J Clin Invest. 2007 Jul;117(7):1988-94
references: 17607367
references: Am J Respir Cell Mol Biol. 2009 Apr;40(4):398-409
references: 18787176
references: Immunology. 1990 Sep;71(1):139-41
references: 2120128
references: Eur J Immunol. 1991 Feb;21(2):431-7
references: 1999225
references: Immunity. 2008 Feb;28(2):271-84
references: 18261937
references: Infect Immun. 1997 May;65(5):1936-8
references: 9125583
references: Clin Exp Immunol. 2004 Aug;137(2):279-87
references: 15270844
references: J Clin Invest. 2004 Feb;113(3):401-13
references: 14755337
references: Cell. 2001 Feb 23;104(4):487-501
references: 11239407
references: J Immunol. 2010 May 1;184(9):4990-9
references: 20304822
references: Clin Exp Immunol. 1993 Oct;94(1):57-63
references: 8403518
references: Tuberculosis (Edinb). 2008 May;88(3):221-34
references: 17950671
references: Infect Immun. 1997 Jun;65(6):2100-6
references: 9169738
references: Infect Immun. 1998 Nov;66(11):5537-42
references: 9784569
references: Rheumatology (Oxford). 2005 Jun;44(6):714-20
references: 15741198
references: J Interferon Cytokine Res. 2006 Jan;26(1):27-33
references: 16426145
references: Infect Immun. 1998 May;66(5):2122-7
references: 9573098
references: J Inflamm. 1995;45(4):221-38
references: 8867667
references: Eur J Immunol. 2001 Jun;31(6):1935-43
references: 11433391
references: J Immunol. 2002 Feb 1;168(3):1328-37
references: 11801673