Trypanosoma cruzi:IL-10, TNF, IFN-γ, and IL-12 Regulate Innate and Acquired Immunity to Infection

• Published in: Experimental parasitology 1996-11, Vol.84 (2), p.231-244
• Main Authors: Abrahamsohn, Ises A., Coffman, Robert L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Cells, Cultured; Chagas Disease - immunology; Chagas Disease - parasitology; Chagas' Disease; Con A, concanavalin A; cytokine regulation of resistance; Dendritic Cells - immunology; Female; IFN-γ; IL-10; IL-10 KO mice, mice with disrupted IL-10 genes; IL-10/RAG KO mice, double KO; IL-12; IL-4; Immunity, Active; Immunity, Innate; innnate and acquired immunity; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Interleukin-12 - biosynthesis; Interleukin-12 - immunology; ip, intraperitoneal; Keratinocytes - immunology; Kinetoplastidae; Lymphocytes - immunology; mAb, monoclonal antibodies; Macrophages - immunology; Male; Mice; Nitrites - metabolism; NO, nitric oxide; Parasitemia; protozoa; RAG KO mice, mice with disrupted recombinase-activating genes; rIL-10, recombinant IL-10; SC, spleen cells; SEM, standard error of the mean; Spleen - cytology; Spleen - immunology; Spleen - metabolism; T-Ag, trypomastigote antigen; TNF; Trypanosoma cruzi; Trypanosoma cruzi - growth & development; Trypanosoma cruzi - immunology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology; WT mice, mice of the same genetic background as the KO but with intact “wild-type” genes
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1006/expr.1996.0109

Control of the acute phase ofTrypanosoma cruziinfections is critically dependent on cytokine-mediated macrophage activation to intracellular killing. We investigated the roles of IL-10, TNF, IFN-γ, and IL-12 in the control of parasitism by innate and specific immunity. Mice with disrupted IL-10 genes (IL-10 KO) infected with Y strainT. cruzihave lower parasite numbers in the blood and tissues and higher IFN-γ and nitric oxide (NO) production by spleen cells than wild type (WT) mice. Treatment of IL-10 KO and WT mice with recombinant IL-10 resulted in increased parasitemia. Mice with disrupted recombinase-activating genes (RAG/KO) that lack B and T cells provided a model for determining the importance of innate immunity to resistance. RAG/KO and WT mice had similar parasitemia levels until Day 13 of infection, suggestive of effective control of parasitism by the innate immune system during the early phase of infection; from then on parasitemia was higher in RAG/KO. Double RAG/IL-10 KO mice and RAG/KO mice had superimposable parasitemia curves, indicating that in the absence of T and B cells, endogenous IL-10 does not limit the efficacy of the innate immune system. Treatment of infected RAG/KO, IL-10/KO, and WT mice with anti-IFN-γ, anti-TNF, or anti-IL-12 neutralizing mAbs increased parasitemia levels showing the importance of endogenous production of these cytokines in the control of parasitism by innate and specific immune responses. Spleen cells from anti-IL12-treated WT mice had diminished production of IFN-γ and NO, suggesting that early IFN-γ synthesis is most dependent on IL-12 stimulation.