| Author | Palhares, Karina Kroll | |
| Author | Silvério, Jaline Coutinho | |
| Author | Silva, Andrea Alice da | |
| Author | Michailowsky, Vladimir | |
| Author | Marino, Ana Paula | |
| Author | Silva, Neide Maria | |
| Author | Carvalho, Cristiano Marcelo Espinola | |
| Author | Pinto, Luzia Maria de Oliveira | |
| Author | Gazzinelli, Ricardo Tostes | |
| Author | Vieira, Joseli Lannes | |
| Access date | 2013-07-04T18:08:54Z | |
| Available date | 2013-07-04T18:08:54Z | |
| Document date | 2008 | |
| Citation | PALHARES, Karina Kroll et al. TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockade. Memórias do Instituto Oswaldo Cruz, v. 103, n. 4, p. 375-385, June 2008. | |
| ISSN | 0074-0276 | |
| URI | https://www.arca.fiocruz.br/handle/icict/6650 | |
| Language | eng | en_US |
| Publisher | Instituto Oswaldo Cruz, Ministério da Saúde | |
| Rights | open access | |
| Title | TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockade | en_US |
| Type | Article | |
| DOI | 10.1590/S0074-02762008000400011 | |
| Abstract | In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-α) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-α levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-α, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-α+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-α treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-α-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-α treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório de Imunologia. Niterói, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade de Uberlândia. Instituto de Ciências Biomédicas. Departamento de Morfologia. Uberlândia, MG, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil. | |
| Subject | Heart disease | en_US |
| Subject | Inflammation | en_US |
| Subject | Trypanosoma cruzi | en_US |
| Subject | CCR5 | en_US |
| Subject | TNFR1 | en_US |
| Subject | TNF-α | en_US |
| e-ISSN | 1678-8060 | |
