Use este identificador para citar ou linkar para este item:
https://www.arca.fiocruz.br/handle/icict/20797
Tipo de documento
ArtigoDireito Autoral
Acesso restrito
Data de embargo
2030-01-01
Objetivos de Desenvolvimento Sustentável
03 Saúde e Bem-EstarColeções
- IOC - Artigos de Periódicos [12747]
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PERFORIN-EXPRESSING CYTOTOXIC CELLS CONTRIBUTE TO CHRONIC CARDIOMYOPATHY IN TRYPANOSOMA CRUZI INFECTION
Chagas Disease
CD8+ T-cells
cytokines
Trypanosoma cruzi
perforin
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil / Universidade Federal Fluminense. Departamento de Patologia. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil / Universidade Federal Fluminense. Departamento de Patologia. Niterói, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.
Resumo em Inglês
Understanding the dual participation of the immune response in controlling the invader and at the same time causing tissue damage might contribute to the design of effective new vaccines and therapies for Chagas disease. Perforin, a cytolytic protein product of killer cells, is involved in resistance to acute Trypanosoma cruzi infection. However, the contribution of perforin in parasite control and chronic chagasic cardiomyopathy is unclear. Perforin-positive cells were detected in the heart tissue during the acute and chronic phases of infection of C57BL/6 mice inoculated with low dose (10(2) parasites) of the Colombian T. cruzi strain. This protocol led to acute phase survival in both wild-type and perforin null (pfp(-/-)) mice lineages. During the chronic infection, parasitism and inducible nitric oxide synthase (iNOS) as well as interleukin (IL)-4+ and, mainly, interferon (IFN)-gamma+ cells were more elevated in the heart tissue of pfp(-/-) mice. Higher levels of circulating NO and anti-parasite immunoglobulin (Ig)G2c and IgG3, paralleled by a prominent frequency of IFN-gamma+ and IL-10+ splenocytes, were present in pfp(-/-)-infected mice. Therefore, although the perforin-dependent pathway plays a role, it is not crucial for anti-T. cruzi immunity and acute phase survival of mice infected with a low inoculum. Further, perforin deficiency resulted in lower activity of creatine kinase-muscle brain isoform (CK-MB) isoenzyme in serum and a more restricted connexin 43 loss, both of which are markers of the cardiomyocyte lesion. Moreover, perforin deficiency hampered the development of severe electrocardiographic abnormalities. Hence, our results corroborate that perforin-bearing cytotoxic cells might contribute to cardiomyocyte lesion and heart dysfunction during chronic T. cruzi infection, shedding light on immunopathogenesis of chronic chagasic cardiomyopathy.
Palavras-chave em inglês
cardiomyopathyChagas Disease
CD8+ T-cells
cytokines
Trypanosoma cruzi
perforin
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