Linked Life Data

8932773

Source:http://linkedlifedata.com/resource/pubmed/id/8932773

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pubmed-article:8932773pubmed:abstractTextControl of the acute phase of Trypanosoma cruzi infections is critically dependent on cytokine-mediated macrophage activation to intracellular killing. We investigated the roles of IL-10, TNF, IFN-gamma, 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 strain T. cruzi have lower parasite numbers in the blood and tissues and higher IFN-gamma 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 them 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-gamma, 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-IL 12-treated WT mice had diminished production of IFN-gamma and NO, suggesting that early IFN-gamma synthesis is most dependent on IL-12 stimulation.lld:pubmed
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pubmed-article:8932773pubmed:articleTitleTrypanosoma cruzi: IL-10, TNF, IFN-gamma, and IL-12 regulate innate and acquired immunity to infection.lld:pubmed
pubmed-article:8932773pubmed:affiliationDepartamento de Imunologia, Universidade de Säo Paulo, Brasil.lld:pubmed
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pubmed-article:8932773pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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