Trypanosoma cruzi: IL-10, TNF, IFN-gamma, and IL-12 regulate innate and acquired immunity to infection

Exp Parasitol. 1996 Nov;84(2):231-44. doi: 10.1006/expr.1996.0109.

Abstract

Control 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cells, Cultured
  • Chagas Disease / immunology*
  • Chagas Disease / parasitology
  • Dendritic Cells / immunology
  • Female
  • Immunity, Active
  • Immunity, Innate
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology*
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology*
  • Keratinocytes / immunology
  • Lymphocytes / immunology
  • Macrophages / immunology
  • Male
  • Mice
  • Nitrites / metabolism
  • Parasitemia
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Trypanosoma cruzi / growth & development
  • Trypanosoma cruzi / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies, Monoclonal
  • Nitrites
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma