dc.creator | Palhares, Karina Kroll | |
dc.creator | Silvério, Jaline Coutinho | |
dc.creator | Silva, Andrea Alice da | |
dc.creator | Michailowsky, Vladimir | |
dc.creator | Marino, Ana Paula | |
dc.creator | Silva, Neide Maria | |
dc.creator | Carvalho, Cristiano Marcelo Espinola | |
dc.creator | Pinto, Luzia Maria de Oliveira | |
dc.creator | Gazzinelli, Ricardo Tostes | |
dc.creator | Vieira, Joseli Lannes | |
dc.date | 2013-07-04T18:08:54Z | |
dc.date | 2013-07-04T18:08:54Z | |
dc.date | 2008 | |
dc.date.accessioned | 2023-09-26T23:25:48Z | |
dc.date.available | 2023-09-26T23:25:48Z | |
dc.identifier | 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. | |
dc.identifier | https://www.arca.fiocruz.br/handle/icict/6650 | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8890481 | |
dc.description | 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 | |
dc.format | application/pdf | |
dc.language | eng | |
dc.rights | open access | |
dc.subject | heart disease | |
dc.subject | inflammation | |
dc.subject | Trypanosoma cruzi | |
dc.subject | CCR5 | |
dc.subject | TNFR1 | |
dc.subject | TNF-α | |
dc.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 | |
dc.type | Article | |