Interleukin-12 but not interleukin-18 is required for immunity to Trypanosoma cruzi in mice.
Protective immunity to the parasite Trypanosoma cruzi in mice depends on a pro-inflammatory T cell response involving the production of interferon-gamma (IFN-gamma). In conjunction with interleukin-12 (IL-12), IL-18 promotes the synthesis of IFN-gamma and a T helper type 1 immune response. We investigated the requirements of IL-12 and IL-18 in murine T. cruzi infection by use of C57BL/6 mice genetically deficient in either cytokine. IL-12p40(-/-) mice succumbed to infection at doses of 100 parasites, whereas IL-18(-/-) and wild-type mice resisted infectious doses up to 1000 parasites to the same extent. Levels of parasitemia were comparable between the latter groups, as were tissue parasite burdens according to quantitative real-time PCR. In contrast, IL-12p40(-/-) mice displayed vastly increased levels of parasites both in blood and in tissue. IFN-gamma concentrations in the serum of infected mice and in supernatants of splenocytes stimulated in vitro were decreased in IL-18(-/-) mice, whereas in IL-12p40(-/-) mice, IFN-gamma was undetectable in the serum and drastically reduced in cell supernatants. Levels of IL-12 production were generally comparable between wild-type and IL-18(-/-) mice, as were levels of IL-4, IL-2 and nitric oxide. Thus, the requirement for endogenous pro-inflammatory cytokines for a protective murine immune response against T. cruzi is satisfied by the expression of IL-12, while IL-18 is dispensable.
Graefe
Sebastian E B
SE
Department for Medical Microbiology and Immunology, Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany. seb@bni-hamburg.de
Jacobs
Thomas
T
Gaworski
Iris
I
Klauenberg
Ulricke
U
Steeg
Christiane
C
Fleischer
Bernhard
B
D000818:Animals; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency / Q000276:immunology*; D020382:Interleukin-18 / Q000172:deficiency / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood; D008099:Liver / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009132:Muscles / Q000469:parasitology; D009569:Nitric Oxide / Q000097:blood; D018512:Parasitemia; D013154:Spleen / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D020382:Interleukin-18; D018664:Interleukin-12; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma