Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.
Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-alpha (TNF alpha) contributes to this disease using murine models in which the action of TNF alpha is inhibited. TNF alpha was neutralized in vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNF alpha or TNF receptor. TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.
Flynn
J L
JL
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Goldstein
M M
MM
Chan
J
J
Triebold
K J
KJ
Pfeffer
K
K
Lowenstein
C J
CJ
Schreiber
R
R
Mak
T W
TW
Bloom
B R
BR
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000209:etiology; D007114:Immunization; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019001:Nitric Oxide Synthase; D016133:Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001500:BCG Vaccine; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases