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https://www.arca.fiocruz.br/handle/icict/7844
IL-10 LIMITS PARASITE BURDEN AND PROTECTS AGAINST FATAL MYOCARDITIS IN A MOUSE MODEL OF TRYPANOSOMA CRUZI INFECTION
Interleukin-10/deficiency
Interleukin-10/physiology
Mice, Inbred C3H
Myocarditis/parasitology
Myocarditis/prevention & control
Author
Affilliation
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Molecular Immunology. Molecular Signaling Section. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA/Karolinska Institutet. Department of Microbiology. Tumor and Cell Biology. Stockholm, Sweden
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Helminth Immunology Section. Bethesda, MD, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Molecular Immunology. Molecular Signaling Section. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Intracellular Parasite Biology Section. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. O Office of the Director. ffice of Research Services. Division of Veterinary Resources. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Molecular Immunology. Molecular Signaling Section. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA/Karolinska Institutet. Department of Microbiology. Tumor and Cell Biology. Stockholm, Sweden
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Helminth Immunology Section. Bethesda, MD, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Molecular Immunology. Molecular Signaling Section. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Intracellular Parasite Biology Section. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. O Office of the Director. ffice of Research Services. Division of Veterinary Resources. Bethesda, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Molecular Immunology. Molecular Signaling Section. Bethesda, MD, USA
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.
Keywords
Chagas Disease/mortalityInterleukin-10/deficiency
Interleukin-10/physiology
Mice, Inbred C3H
Myocarditis/parasitology
Myocarditis/prevention & control
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