Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection.
During a sublethal murine infection with Listeria monocytogenes cells, tumor necrosis factor (TNF) activity was detectable in neither sera nor spleen homogenates at any stage of the infection when a bioassay with L-929 cells (less than 4 U/ml) was used. However, injecting the mice with an immunoglobulin fraction obtained from a rabbit hyperimmunized with recombinant murine TNF-alpha resulted in acceleration of listeriosis. When 1 mg of anti-TNF antibody was injected per mouse, all the mice died from listeriosis, even though the infectious dose was sublethal for the untreated controls. The antigen-specific elimination of the bacterium from the spleens and livers of anti-TNF antibody-treated mice was delayed, depending on the dose of the antibody injected. Endogenous TNF seemed to be produced early in infection, because suppression of antilisterial resistance was significant when a single injection of anti-TNF antibody was given between day zero and day 2 of infection. The effect of endogenous TNF on antilisterial resistance was due to neither regulation of alpha interferon (IFN-alpha) and IFN-gamma production nor induction of IFN-beta subtype 1 (IFN-beta 1), because anti-TNF antibody treated-mice produced normal levels of IFN-alpha and IFN-gamma in the bloodstream during infection and administration of monoclonal anti-murine IFN-beta 1 antibody had no effect on the development of listeriosis. Alternatively, the listericidal activity of peritoneal macrophages of L. monocytogenes-infected mice could be abrogated by injection of anti-TNF antibody in vivo. These results suggest that the lower level of TNF is produced endogenously in mice that received L. monocytogenes infection and that it plays an essential role in the host defense against L. monocytogenes infection.
D000818:Animals; D000937:Antigen-Antibody Reactions; D007111:Immunity, Cellular; D007158:Immunologic Techniques; D007370:Interferon Type I / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D008088:Listeriosis / Q000276:immunology* / Q000503:physiopathology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma