Control of IL-12 and IFN-gamma production in response to live or dead bacteria by TNF and other factors.
When mice were infected i.v. with either Listeria monocytogenes or Brucella abortus, bioactive IL-12 was briefly detected in serum and supernatants of spleen homogenates immediately ex vivo. Although the time scale was more prolonged for the more slowly growing B. abortus, in both instances IL-12 production ceased while bacteria still persisted in high numbers. Production of IL-12, detected in serum and spleen, was neither increased nor prolonged by injecting Abs to IL-10 or IL-4. In contrast with live organisms, heat-killed bacteria did not induce detectable IL-12 in vivo and were less efficient when added in vitro to resident peritoneal cells or spleen cells. Mice lacking the receptors for TNF (TNFR-/- mice) were severely deficient in IL-12 production, suggesting a controlling role for TNF, which we have previously shown to be triggered by live, rather than dead, bacteria. Infection in the TNFR-/- mice was exacerbated, although in the Brucella-infected mice splenomegaly, the main indicator of immunopathology, was reduced. Production of NO by macrophages was deficient, but the TNFR-/- mice were not deficient in IFN-gamma production. In addition to being poor inducers of IL-12, killed bacteria actively suppressed IL-12 production in response to live bacteria, by mechanism(s) unknown. The implications of these findings are discussed in light of the fact that only live bacteria satisfactorily induce cell-mediated immunity to infection.
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
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D000818:Animals; D002004:Brucella Vaccine / Q000276:immunology; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D006358:Hot Temperature; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000502:physiology; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014613:Vaccines, Attenuated / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology*
D002004:Brucella Vaccine; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma