Involvement of cytokines in determining resistance and acquired immunity in murine tuberculosis.
Herein we demonstrate that continuous infusion of either TNF-alpha or IFN-gamma (10(4) U/day) via osmotic micropumps leads to an increased resistance of mice infected with a lethal dose (10(7)) of M. tuberculosis H37Rv, associated with a decreased microbial growth in all target organs. This result was reinforced by the finding that infusion of antibodies against TNF-alpha or IFN-gamma greatly enhanced susceptibility of naive mice to tuberculosis. In a final set of experiments, using neutralizing antibodies, we show that IFN-gamma, not TNF-alpha is involved in determining acquired resistance against murine tuberculosis, as seen by the fact that acquired immunity is resistant to anti-TNF-alpha antibodies, yet sensitive to anti-IFN-gamma antibodies. This suggests a role for both IFN-gamma and TNF-alpha in determining innate resistance whereas IFN-gamma may be the mediator of the anamnestic response.
Denis
M
M
Unité de Recherche, Centre de Pneumologie, Hôpital Laval, Ste-Foy, Québec, Canada.
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016207:Cytokines / Q000502:physiology* / Q000627:therapeutic use; D007113:Immunity, Innate / Q000276:immunology* / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology / Q000627:therapeutic use; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology / Q000627:therapeutic use
D000914:Antibodies, Viral; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma