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
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2008 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/6650 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil |
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Palhares, Karina KrollSilvério, Jaline CoutinhoSilva, Andrea Alice daMichailowsky, VladimirMarino, Ana PaulaSilva, Neide MariaCarvalho, Cristiano Marcelo EspinolaPinto, Luzia Maria de OliveiraGazzinelli, Ricardo TostesVieira, Joseli Lannes2013-07-04T18:08:54Z2013-07-04T18:08:54Z2008KROLL PALHARES, Karina 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. Mem Inst Oswaldo Cruz. 2008 Jun;103(4):375-85.https://www.arca.fiocruz.br/handle/icict/6650engTNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockadeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, BrasilUniversidade Federal Fluminense. Departamento de Patologia. Laboratório de Imunologia. Niterói, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, BrasilUniversidade de Uberlândia. Instituto de Ciências Biomédicas. Departamento de Morfologia. Uberlândia, MG, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, BrasilIn 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 cardiomyopathyheart diseaseinflammationTrypanosoma cruziCCR5TNFR1TNF-αinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINAL82. KROLL-PALHARES K.pdf82. KROLL-PALHARES K.pdfapplication/pdf3108378https://www.arca.fiocruz.br/bitstream/icict/6650/1/82.%20KROLL-PALHARES%20K.pdfcf48803ab9ca0b05036407ac851dd43cMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/6650/2/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD52TEXT82. KROLL-PALHARES K.pdf.txt82. 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| dc.title.pt_BR.fl_str_mv |
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 |
| 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 |
| spellingShingle |
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 Palhares, Karina Kroll heart disease inflammation Trypanosoma cruzi CCR5 TNFR1 TNF-α |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| author |
Palhares, Karina Kroll |
| author_facet |
Palhares, Karina Kroll Silvério, Jaline Coutinho Silva, Andrea Alice da Michailowsky, Vladimir Marino, Ana Paula Silva, Neide Maria Carvalho, Cristiano Marcelo Espinola Pinto, Luzia Maria de Oliveira Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes |
| author_role |
author |
| author2 |
Silvério, Jaline Coutinho Silva, Andrea Alice da Michailowsky, Vladimir Marino, Ana Paula Silva, Neide Maria Carvalho, Cristiano Marcelo Espinola Pinto, Luzia Maria de Oliveira Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Palhares, Karina Kroll Silvério, Jaline Coutinho Silva, Andrea Alice da Michailowsky, Vladimir Marino, Ana Paula Silva, Neide Maria Carvalho, Cristiano Marcelo Espinola Pinto, Luzia Maria de Oliveira Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes |
| dc.subject.en.pt_BR.fl_str_mv |
heart disease inflammation Trypanosoma cruzi CCR5 TNFR1 TNF-α |
| topic |
heart disease inflammation Trypanosoma cruzi CCR5 TNFR1 TNF-α |
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Auto-imunidade e Imuno-regulação. Rio de Janeiro, RJ, Brasil |
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2008 |
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2008 |
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2013-07-04T18:08:54Z |
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2013-07-04T18:08:54Z |
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info:eu-repo/semantics/article |
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article |
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KROLL PALHARES, Karina 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. Mem Inst Oswaldo Cruz. 2008 Jun;103(4):375-85. |
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https://www.arca.fiocruz.br/handle/icict/6650 |
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KROLL PALHARES, Karina 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. Mem Inst Oswaldo Cruz. 2008 Jun;103(4):375-85. |
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