Chagas cardiomyopathy is associated with a high susceptibility to T. cruzi infection in monocyte-derived macrophages and a predominance of CD4+CD45RO+ T-cells with immunoregulatory patterns

Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Universidade Federal de Viçosa. Departamento de Bioquímica e Biologia Molecular. Viçosa, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil. Universidade Federal de Minas Gerais. Colégio Técnico. Departamento de Patologia Clínica. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil. Universidade Federal de Minas Gerais. Colégio Técnico. Departamento de Patologia Clínica. Belo Horizonte, MG, Brazil.

Abstract

The pathogenesis of Chronic Chagas Cardiomyopathy (CCC) is still not fully understood, and the persistence of the parasite in tissues seems to be essential for the onset and progression of heart disease, tissue destruction, and chronic inflammation. It is clear that the polarity found between the asymptomatic (IND) and cardiac clinical forms refers mainly to the mechanisms involved in the regulation of the host's immune response. Thus, to elucidate aspects of the susceptibility of host phagocytes to T. cruzi infection, the present study explored novel aspects of innate immune response, integrating data on susceptibility to infection and intracellular replication, using monocyte-derived macrophages from CCC patients, together with memory CD4+ T-cells (CD45RO+). The isolation of PBMC was conducted by means of in vitro infection assay with T. cruzi trypomastigotes and flow cytometry analysis of the intracytoplasmic cytokine production by CD4+T-cells. Our findings indicated that monocytes derived from individuals with CCC are more susceptible to the infection and replication of intracellular amastigotes. Moreover, the stimulation of CD4+ T-cells from CCC patients, together with T. cruzi trypomastigotes, induces a predominance of a regulatory response over a type 1 response, demonstrated by an increase in IL-10 production and a reduction in the IFN-γ and IFN-γ/IL-10. Suppression of the function of monocyte-derived macrophages, from CCC patients, to control trypomastigote infection and intracellular replication sheds light on a potential susceptibility of these cells isolated from peripheral blood, which may reflect the ineffectiveness of parasite control by phagocytes in cardiac tissues, which can subsequently result in serious heart disease.

Keywords

CD4(+) T-cells
Chagas’ disease
Chronic chagas cardiomyopathy
IFN-γ
IL-10 cytokines
Monocyte-derived macrophage
T. cruzi trypomastigotes

Publisher

Elsevier

Citation

CARVALHO, Ana Maria Ravena Severino et al. Chagas cardiomyopathy is associated with a high susceptibility to T. cruzi infection in monocyte-derived macrophages and a predominance of CD4+ CD45RO+ T-cells with immunoregulatory patterns. Acta Tropica, v. 237, p. 106749, 2023. Doi: 10.1016/j.actatropica.2022.106749

ISSN

0001-706X

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/56650

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Copyright

Restricted access

Embargo date

2099-12-31

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