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*
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia;
Department of Medicine, University of Sydney, Sydney New South Wales, Australia; and
Department of Veterinary Anatomy and Pathology, University of Sydney, Sydney, New South Wales, Australia
TNF and lymphotoxin-
(LT) may act at various stages of the
host response to Mycobacterium tuberculosis. To dissect
the effects of TNF independent of LT, we have used C57BL/6 mice with
a disruption of the TNF gene alone (TNF-/-). Twenty-one
days following aerosol M. tuberculosis infection there
was a marked increase in the number of organisms in the lungs of
TNF-/- mice, and by 28–35 days all animals had
succumbed, with widespread dissemination of M.
tuberculosis. In comparison with the localized granulomas
containing activated macrophages and T cells in lungs and livers of
C57BL/6 wild-type (wt) mice, cellular infiltrates in
TNF-/- mice were poorly formed, with extensive regions of
necrosis and neutrophilic infiltration of the alveoli. Phenotypic
analysis of lung homogenates demonstrated similar numbers of
CD4+ and CD8+ T cells in TNF-/-
and wt mice, but in TNF-deficient mice the lymphocytes were restricted
to perivascular and peribronchial areas rather than colocated with
macrophages in granulomas. T cells from TNF-/- mice
retained proliferative and cytokine responses to purified protein
derivative, and delayed-type hypersensitivity to purified protein
derivative was demonstrable. Macrophages within the lungs of
TNF-/- and wt mice showed similar levels of MHC class II
and inducible nitric oxide synthase expression, and levels of serum
nitrite were comparable. Thus, the enhanced susceptibility of
TNF-/- is not compensated for by the presence of LT,
and the critical role of TNF is not in the activation of T cells and
macrophages but in the local organization of
granulomas.
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S Ehlers Role of tumour necrosis factor (TNF) in host defence against tuberculosis: implications for immunotherapies targeting TNF Ann Rheum Dis, November 1, 2003; 62(90002): ii37 - 42. [Abstract] [Full Text] [PDF]
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S. Ehlers, C. Holscher, S. Scheu, C. Tertilt, T. Hehlgans, J. Suwinski, R. Endres, and K. Pfeffer The Lymphotoxin {beta} Receptor Is Critically Involved in Controlling Infections with the Intracellular Pathogens Mycobacterium tuberculosis and Listeria monocytogenes J. Immunol., May 15, 2003; 170(10): 5210 - 5218. [Abstract] [Full Text] [PDF]
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 R. Barthel, A. V. Tsytsykova, A. K. Barczak, E. Y. Tsai, C. C. Dascher, M. B. Brenner, and A. E. Goldfeld Regulation of Tumor Necrosis Factor Alpha Gene Expression by Mycobacteria Involves the Assembly of a Unique Enhanceosome Dependent on the Coactivator Proteins CBP/p300 Mol. Cell. Biol., January 15, 2003; 23(2): 526 - 533. [Abstract] [Full Text] [PDF]
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C. A. Murphy, R. M. Hoek, M. T. Wiekowski, S. A. Lira, and J. D. Sedgwick Interactions Between Hemopoietically Derived TNF and Central Nervous System-Resident Glial Chemokines Underlie Initiation of Autoimmune Inflammation in the Brain J. Immunol., December 15, 2002; 169(12): 7054 - 7062. [Abstract] [Full Text] [PDF]
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H. M. Scott and J. L. Flynn Mycobacterium tuberculosis in Chemokine Receptor 2-Deficient Mice: Influence of Dose on Disease Progression Infect. Immun., November 1, 2002; 70(11): 5946 - 5954. [Abstract] [Full Text] [PDF]
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 H.-S. Choi, P. R. Rai, H. W. Chu, C. Cool, and E. D. Chan Analysis of Nitric Oxide Synthase and Nitrotyrosine Expression in Human Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 178 - 186. [Abstract] [Full Text] [PDF]
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D. R. Roach, A. G. D. Bean, C. Demangel, M. P. France, H. Briscoe, and W. J. Britton TNF Regulates Chemokine Induction Essential for Cell Recruitment, Granuloma Formation, and Clearance of Mycobacterial Infection J. Immunol., May 1, 2002; 168(9): 4620 - 4627. [Abstract] [Full Text] [PDF]
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 R. van Crevel, T. H. M. Ottenhoff, and J. W. M. van der Meer Innate Immunity to Mycobacterium tuberculosis Clin. Microbiol. Rev., April 1, 2002; 15(2): 294 - 309. [Abstract] [Full Text] [PDF]
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S. Smith, D. Liggitt, E. Jeromsky, X. Tan, S. J. Skerrett, and C. B. Wilson Local Role for Tumor Necrosis Factor Alpha in the Pulmonary Inflammatory Response to Mycobacterium tuberculosis Infection Infect. Immun., April 1, 2002; 70(4): 2082 - 2089. [Abstract] [Full Text] [PDF]
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M. L. Olleros, R. Guler, N. Corazza, D. Vesin, H.-P. Eugster, G. Marchal, P. Chavarot, C. Mueller, and I. Garcia Transmembrane TNF Induces an Efficient Cell-Mediated Immunity and Resistance to Mycobacterium bovis Bacillus Calmette-Guerin Infection in the Absence of Secreted TNF and Lymphotoxin-{alpha} J. Immunol., April 1, 2002; 168(7): 3394 - 3401. [Abstract] [Full Text] [PDF]
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R. Lang, R. L. Rutschman, D. R. Greaves, and P. J. Murray Autocrine Deactivation of Macrophages in Transgenic Mice Constitutively Overexpressing IL-10 Under Control of the Human CD68 Promoter J. Immunol., April 1, 2002; 168(7): 3402 - 3411. [Abstract] [Full Text] [PDF]
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U. Palendira, A. G. D. Bean, C. G. Feng, and W. J. Britton Lymphocyte Recruitment and Protective Efficacy against Pulmonary Mycobacterial Infection Are Independent of the Route of Prior Mycobacterium bovis BCG Immunization Infect. Immun., March 1, 2002; 70(3): 1410 - 1416. [Abstract] [Full Text] [PDF]
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 W. S. Lim, R.J. Powell, I.D. Johnston, Z. Zhang, H. Correa, R. E. Begue, F. G. De Rosa, S. Bonora, G. Di Perri, A. Myers, et al. Tuberculosis and Treatment with Infliximab N. Engl. J. Med., February 21, 2002; 346(8): 623 - 626. [Full Text] [PDF]
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M. Engele, K. Castiglione, N. Schwerdtner, M. Wagner, P. Bolcskei, M. Rollinghoff, and S. Stenger Induction of TNF in Human Alveolar Macrophages As a Potential Evasion Mechanism of Virulent Mycobacterium tuberculosis J. Immunol., February 1, 2002; 168(3): 1328 - 1337. [Abstract] [Full Text] [PDF]
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N. P. Juffermans, J. C. Leemans, S. Florquin, A. Verbon, A. H. Kolk, P. Speelman, S. J. H. van Deventer, and T. van der Poll CpG Oligodeoxynucleotides Enhance Host Defense during Murine Tuberculosis Infect. Immun., January 1, 2002; 70(1): 147 - 152. [Abstract] [Full Text] [PDF]
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W. Peters, H. M. Scott, H. F. Chambers, J. L. Flynn, I. F. Charo, and J. D. Ernst Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis PNAS, July 3, 2001; 98(14): 7958 - 7963. [Abstract] [Full Text] [PDF]
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J. L. Flynn and J. Chan Tuberculosis: Latency and Reactivation Infect. Immun., July 1, 2001; 69(7): 4195 - 4201. [Full Text] [PDF]
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Z. Xing, A. Zganiacz, J. Wang, and S. K. Sharma Enhanced Protection Against Fatal Mycobacterial Infection in SCID Beige Mice by Reshaping Innate Immunity with IFN-{{gamma}} Transgene J. Immunol., July 1, 2001; 167(1): 375 - 383. [Abstract] [Full Text] [PDF]
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L.-G. Bekker, S. Freeman, P. J. Murray, B. Ryffel, and G. Kaplan TNF-{{alpha}} Controls Intracellular Mycobacterial Growth by Both Inducible Nitric Oxide Synthase-Dependent and Inducible Nitric Oxide Synthase-Independent Pathways J. Immunol., June 1, 2001; 166(11): 6728 - 6734. [Abstract] [Full Text] [PDF]
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N. Boechat, F. Bouchonnet, M. Bonay, A. Grodet, V. Pelicic, B. Gicquel, and A. J. Hance Culture at High Density Improves the Ability of Human Macrophages to Control Mycobacterial Growth J. Immunol., May 15, 2001; 166(10): 6203 - 6211. [Abstract] [Full Text] [PDF]
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C. Demangel, U. Palendira, C. G. Feng, A. W. Heath, A. G. D. Bean, and W. J. Britton Stimulation of Dendritic Cells via CD40 Enhances Immune Responses to Mycobacterium tuberculosis Infection Infect. Immun., April 1, 2001; 69(4): 2456 - 2461. [Abstract] [Full Text] [PDF]
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C. Ameixa and J. S. Friedland Down-Regulation of Interleukin-8 Secretion from Mycobacterium tuberculosis-Infected Monocytes by Interleukin-4 and -10 but Not by Interleukin-13 Infect. Immun., April 1, 2001; 69(4): 2470 - 2476. [Abstract] [Full Text] [PDF]
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P. Wilhelm, U. Ritter, S. Labbow, N. Donhauser, M. Rollinghoff, C. Bogdan, and H. Korner Rapidly Fatal Leishmaniasis in Resistant C57BL/6 Mice Lacking TNF J. Immunol., March 15, 2001; 166(6): 4012 - 4019. [Abstract] [Full Text] [PDF]
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T. K. Means, B. W. Jones, A. B. Schromm, B. A. Shurtleff, J. A. Smith, J. Keane, D. T. Golenbock, S. N. Vogel, and M. J. Fenton Differential Effects of a Toll-Like Receptor Antagonist on Mycobacterium tuberculosis-Induced Macrophage Responses J. Immunol., March 15, 2001; 166(6): 4074 - 4082. [Abstract] [Full Text] [PDF]
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F. A. Post, C. Manca, O. Neyrolles, B. Ryffel, D. B. Young, and G. Kaplan Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Mycobacterium smegmatis-Induced Cytokine Production by Human Macrophages In Vitro Infect. Immun., March 1, 2001; 69(3): 1433 - 1439. [Abstract] [Full Text] [PDF]
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V. P. Mohan, C. A. Scanga, K. Yu, H. M. Scott, K. E. Tanaka, E. Tsang, M. C. Tsai, J. L. Flynn, and J. Chan Effects of Tumor Necrosis Factor Alpha on Host Immune Response in Chronic Persistent Tuberculosis: Possible Role for Limiting Pathology Infect. Immun., March 1, 2001; 69(3): 1847 - 1855. [Abstract] [Full Text] [PDF]
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J. E. Wigginton and D. Kirschner A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis J. Immunol., February 1, 2001; 166(3): 1951 - 1967. [Abstract] [Full Text] [PDF]
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D. R. Roach, H. Briscoe, B. Saunders, M. P. France, S. Riminton, and W. J. Britton Secreted Lymphotoxin-{alpha} Is Essential for the Control of an Intracellular Bacterial Infection J. Exp. Med., January 15, 2001; 193(2): 239 - 246. [Abstract] [Full Text] [PDF]
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A. M. Cooper, J. E. Pearl, J. V. Brooks, S. Ehlers, and I. M. Orme Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung Infect. Immun., December 1, 2000; 68(12): 6879 - 6882. [Abstract] [Full Text] [PDF]
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L.-G. Bekker, A. L. Moreira, A. Bergtold, S. Freeman, B. Ryffel, and G. Kaplan Immunopathologic Effects of Tumor Necrosis Factor Alpha in Murine Mycobacterial Infection Are Dose Dependent Infect. Immun., December 1, 2000; 68(12): 6954 - 6961. [Abstract] [Full Text] [PDF]
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H. W. Murray, A. Jungbluth, E. Ritter, C. Montelibano, and M. W. Marino Visceral Leishmaniasis in Mice Devoid of Tumor Necrosis Factor and Response to Treatment Infect. Immun., November 1, 2000; 68(11): 6289 - 6293. [Abstract] [Full Text] [PDF]
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H. Briscoe, D. R. Roach, N. Meadows, D. Rathjen, and W. J. Britton A novel tumor necrosis factor (TNF) mimetic peptide prevents recrudescence of Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection in CD4+ T cell-depleted mice J. Leukoc. Biol., October 1, 2000; 68(4): 538 - 544. [Abstract] [Full Text]
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