| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Division of Molecular Infection Biology, Research Center Borstel, Borstel, Germany;
Department of Anatomy, Medical University of Lübeck, Lübeck, Germany; and
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
Genetically susceptible, TNFRp55 gene-deficient
(TNFRp55-/-) mice succumb to infection with
Mycobacterium avium. Before their death, M.
avium-infected TNFRp55-/- mice
develop granulomatous lesions that, in contrast to granulomas in
wild-type syngeneic mice, undergo acute disintegration. To determine
the factors involved in these events, we depleted T cell subsets
or neutralized the inflammatory cytokines IFN-
, IL-12, or TNF
in TNFRp55-/- mice infected i.v. with
M. avium. Infected TNFRp55-/-
mice treated with a control mAb became moribund between days 26 and 34
postinfection, showing widespread inflammatory cell apoptosis within
disintegrating granulomas. In contrast,
TNFRp55-/- mice depleted of either
CD4+ or CD8+ cells after granuloma initiation
stayed healthy until at least day 38 postinfection and showed no signs
of granuloma destruction. Neutralization of IL-12, but not of IFN-
or TNF, also protected M. avium-infected
TNFRp55-/- mice from granuloma decomposition
and from premature death. Treatment with dexamethasone or with a
specific inhibitor of inducible NO synthase did not prevent granuloma
dissolution or death of TNFRp55-/- mice. In
conclusion, granuloma disintegration in
TNFRp55-/- mice is a lethal event that is
dependent on IL-12 and that is mediated by an excess of T
cells.
This article has been cited by other articles:
|
|
 |
|
  M. Schaefer, N. Reiling, C. Fessler, J. Stephani, I. Taniuchi, F. Hatam, A. O. Yildirim, H. Fehrenbach, K. Walter, J. Ruland, et al. Decreased Pathology and Prolonged Survival of Human DC-SIGN Transgenic Mice during Mycobacterial Infection J. Immunol., May 15, 2008; 180(10): 6836 - 6845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rottman, E. Catherinot, P. Hochedez, J.-F. Emile, J.-L. Casanova, J.-L. Gaillard, and C. Soudais Importance of T Cells, Gamma Interferon, and Tumor Necrosis Factor in Immune Control of the Rapid Grower Mycobacterium abscessus in C57BL/6 Mice Infect. Immun., December 1, 2007; 75(12): 5898 - 5907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Florido and R. Appelberg Characterization of the Deregulated Immune Activation Occurring at Late Stages of Mycobacterial Infection in TNF-Deficient Mice J. Immunol., December 1, 2007; 179(11): 7702 - 7708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Cowley, J. D. Sedgwick, and K. L. Elkins Differential Requirements by CD4+ and CD8+ T Cells for Soluble and Membrane TNF in Control of Francisella tularensis Live Vaccine Strain Intramacrophage Growth J. Immunol., December 1, 2007; 179(11): 7709 - 7719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. V. Kondratieva, V. V. Evstifeev, T. K. Kondratieva, S. N. Petrovskaya, A. V. Pichugin, E. I. Rubakova, M. M. Averbakh Jr., and A. S. Apt I/St Mice Hypersusceptible to Mycobacterium tuberculosis Are Resistant to M. avium Infect. Immun., October 1, 2007; 75(10): 4762 - 4768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Musicki, H. Briscoe, S. Tran, W. J. Britton, and B. M. Saunders Differential Requirements for Soluble and Transmembrane Tumor Necrosis Factor in the Immunological Control of Primary and Secondary Listeria monocytogenes Infection. Infect. Immun., June 1, 2006; 74(6): 3180 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zakharova and H. K. Ziegler Paradoxical Anti-Inflammatory Actions of TNF-{alpha}: Inhibition of IL-12 and IL-23 via TNF Receptor 1 in Macrophages and Dendritic Cells J. Immunol., October 15, 2005; 175(8): 5024 - 5033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Saunders, S. Tran, S. Ruuls, J. D. Sedgwick, H. Briscoe, and W. J. Britton Transmembrane TNF Is Sufficient to Initiate Cell Migration and Granuloma Formation and Provide Acute, but Not Long-Term, Control of Mycobacterium tuberculosis Infection J. Immunol., April 15, 2005; 174(8): 4852 - 4859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rao, N. Fujiwara, S. A. Porcelli, and M. S. Glickman Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule J. Exp. Med., February 22, 2005; 201(4): 535 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Giles and J. M. Bathon Serious Infections Associated with Anticytokine Therapies in the Rheumatic Diseases J Intensive Care Med, November 1, 2004; 19(6): 320 - 334. [Abstract] [PDF]
|
|
|
|
|
|
M. Florido and R. Appelberg Granuloma Necrosis during Mycobacterium avium Infection Does Not Require Tumor Necrosis Factor Infect. Immun., October 1, 2004; 72(10): 6139 - 6141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. S. Algood, P. L. Lin, D. Yankura, A. Jones, J. Chan, and J. L. Flynn TNF Influences Chemokine Expression of Macrophages In Vitro and That of CD11b+ Cells In Vivo during Mycobacterium tuberculosis Infection J. Immunol., June 1, 2004; 172(11): 6846 - 6857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Coussens, N. Verman, M. A. Coussens, M. D. Elftman, and A. M. McNulty Cytokine Gene Expression in Peripheral Blood Mononuclear Cells and Tissues of Cattle Infected with Mycobacterium avium subsp. paratuberculosis: Evidence for an Inherent Proinflammatory Gene Expression Pattern Infect. Immun., March 1, 2004; 72(3): 1409 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 T. D. Nguyen, G. Bigaignon, D. Markine-Goriaynoff, H. Heremans, T. N. Nguyen, G. Warnier, M. Delmee, M. Warny, S. F. Wolf, C. Uyttenhove, et al. Virulent Toxoplasma gondii strain RH promotes T-cell-independent overproduction of proinflammatory cytokines IL12 and {gamma}-interferon J. Med. Microbiol., October 1, 2003; 52(10): 869 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Villarreal-Ramos, M. McAulay, V. Chance, M. Martin, J. Morgan, and C. J. Howard Investigation of the Role of CD8+ T Cells in Bovine Tuberculosis In Vivo Infect. Immun., August 1, 2003; 71(8): 4297 - 4303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Inoue, H. Takano, R. Yanagisawa, T. Yoshikawa, R. Vassallo, E. L. Matteson, and C. F. Thomas Jr. Effects of Tumor Necrosis Factor-{alpha} Inhibitors on Lung Lesions With Rheumatoid Arthritis Chest, July 1, 2003; 124(1): 413 - 414. [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Taylor, R. Orkin, and J. Lanham Tuberculosis following therapy with infliximab may be refractory to antibiotic therapy Rheumatology, July 1, 2003; 42(7): 901 - 902. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Ehlers, J. Benini, H.-D. Held, C. Roeck, G. Alber, and S. Uhlig {alpha}{beta} T Cell Receptor-positive Cells and Interferon-{gamma}, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology J. Exp. Med., December 17, 2001; 194(12): 1847 - 1859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Mansfield, R. S. Veazey, A. Hancock, A. Carville, M. Elliott, K.-C. Lin, and A. A. Lackner Induction of Disseminated Mycobacterium avium in Simian AIDS Is Dependent upon Simian Immunodeficiency Virus Strain and Defective Granuloma Formation Am. J. Pathol., August 1, 2001; 159(2): 693 - 702. [Abstract] [Full Text]
|
|
|
|
|
|
K. Chen, Y. Wei, G. C. Sharp, and H. Braley-Mullen Induction of Experimental Autoimmune Thyroiditis in IL-12-/- Mice J. Immunol., August 1, 2001; 167(3): 1720 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Dietrich Using Mouse Genetics to Understand Infectious Disease Pathogenesis Genome Res., March 1, 2001; 11(3): 325 - 331. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
