title: IL-10 limits parasite burden and protects against fatal myocarditis in a mouse model of Trypanosoma cruzi infection.
abstract: Chagas' disease is a zoonosis prevalent in Latin America that is caused by the protozoan Trypanosoma cruzi. The immunopathogenesis of cardiomyopathy, the main clinical problem in Chagas' disease, has been extensively studied but is still poorly understood. In this study, we systematically compared clinical, microbiologic, pathologic, immunologic, and molecular parameters in two mouse models with opposite susceptibility to acute myocarditis caused by the myotropic Colombiana strain of T. cruzi: C3H/HeSnJ (100% mortality, uncontrolled parasitism) and C57BL/6J (<10% mortality, controlled parasitism). T. cruzi induced differential polarization of immunoregulatory cytokine mRNA expression in the hearts of C57BL/6J versus C3H/HeSnJ mice; however, most differences were small. The difference in IL-10 expression was exceptional (C57BL/6J 8.7-fold greater than C3H/HeSnJ). Consistent with this, hearts from infected C57BL/6J mice, but not C3H/HeSnJ mice, had a high frequency of total IL-10-producing CD8(+) T cells and both CD4(+) and CD8(+) subsets of IFN-γ(+)IL-10(+) double-producing T cells. Furthermore, T. cruzi infection of IL-10(-/-) C57BL/6J mice phenocopied fatal infection in wild-type C3H/HeSnJ mice with complete loss of parasite control. Adoptive transfer experiments indicated that T cells were a source of protective IL-10. Thus, in this system, IL-10 production by T cells promotes T. cruzi control and protection from fatal acute myocarditis.
authors.affiliation: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ester
authors.initials: E
authors.lastname: Roffê
authors.forename: Antonio Gigliotti
authors.initials: AG
authors.lastname: Rothfuchs
authors.forename: Helton C
authors.initials: HC
authors.lastname: Santiago
authors.forename: Ana Paula M P
authors.initials: AP
authors.lastname: Marino
authors.forename: Flavia L
authors.initials: FL
authors.lastname: Ribeiro-Gomes
authors.forename: Michael
authors.initials: M
authors.lastname: Eckhaus
authors.forename: Lis R V
authors.initials: LR
authors.lastname: Antonelli
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D014355:Chagas Disease / Q000401:mortality / Q000469:parasitology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000401:mortality / Q000469:parasitology* / Q000517:prevention & control*; D018512:Parasitemia / Q000276:immunology / Q000401:mortality / Q000469:parasitology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10