Trypanosoma cruzi: IL-10, TNF, IFN-gamma, and IL-12 regulate innate and acquired immunity to infection.
Exp Parasitol
; 84(2): 231-44, 1996 Nov.
Article
en En
| MEDLINE
| ID: mdl-8932773
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
3_ND
Problema de salud:
2_enfermedades_transmissibles
/
3_zoonosis
Asunto principal:
Trypanosoma cruzi
/
Interferón gamma
/
Factor de Necrosis Tumoral alfa
/
Interleucina-10
/
Enfermedad de Chagas
/
Interleucina-12
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Exp Parasitol
Año:
1996
Tipo del documento:
Article
País de afiliación:
Brasil