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https://www.arca.fiocruz.br/handle/icict/51760
PHENOTYPIC AND FUNCTIONAL SIGNATURES OF PERIPHERAL BLOOD AND SPLEEN COMPARTMENTS OF CYNOMOLGUS MACAQUES INFECTED WITH T. CRUZI: ASSOCIATIONS WITH CARDIAC HISTOPATHOLOGICAL CHARACTERISTICS
cardiac Chagas disease
cynomolgus macaques
cytokines
immune response
non-human primates
Author
Affilliation
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States/Faculdade de Minas. Belo Horizonte, MG, Brazil/ Faculdade de Ciências Médicas de Minas Gerais. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States.
Faculdade de Minas. Belo Horizonte, MG, Brazil.
Instituto René Rachou.Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States.
Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States.
Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States/South Texas Diabetes and Obesity Institute and Department of Human Genetics. School of Medicine. The University of Texas Rio Grande Valley. Brownsville/Harlingen/Edinburg, TX, United States/Center for Vector-Borne Diseases. The University of Texas Rio Grande Valley. Brownsville/Harlingen/Edinburg, TX, United States.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States.
Faculdade de Minas. Belo Horizonte, MG, Brazil.
Instituto René Rachou.Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States.
Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States.
Southwest National Primate Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States/South Texas Diabetes and Obesity Institute and Department of Human Genetics. School of Medicine. The University of Texas Rio Grande Valley. Brownsville/Harlingen/Edinburg, TX, United States/Center for Vector-Borne Diseases. The University of Texas Rio Grande Valley. Brownsville/Harlingen/Edinburg, TX, United States.
Instituto René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Abstract
We performed a detailed analysis of immunophenotypic features of circulating leukocytes and spleen cells from cynomolgus macaques that had been naturally infected with Trypanosoma cruzi, identifying their unique and shared characteristics in relation to cardiac histopathological lesion status. T. cruzi-infected macaques were categorized into three groups: asymptomatic [CCC(-)], with mild chronic chagasic cardiopathy [CCC(+)], or with moderate chronic chagasic cardiopathy [CCC(++)]. Our findings demonstrated significant differences in innate and adaptive immunity cells of the peripheral blood and spleen compartments, by comparison with non-infected controls. CCC(+) and CCC(++) hosts exhibited decreased frequencies of monocytes, NK and NKT-cell subsets in both compartments, and increased frequencies of activated CD8+ T-cells and GranA+/GranB+ cells. While a balanced cytokine profile (TNF/IL-10) was observed in peripheral blood of CCC(-) macaques, a predominant pro-inflammatory profile (increased levels of TNF and IFN/IL-10) was observed in both CCC(+) and CCC(++) subgroups. Our data demonstrated that cardiac histopathological features of T. cruzi-infected cynomolgus macaques are associated with perturbations of the immune system similarly to those observed in chagasic humans. These results provide further support for the validity of the cynomolgus macaque model for pre-clinical research on Chagas disease, and provide insights pertaining to the underlying immunological mechanisms involved in the progression of cardiac Chagas disease
Keywords
Trypanosoma cruzicardiac Chagas disease
cynomolgus macaques
cytokines
immune response
non-human primates
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