Brasil | Article

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.creatorPalhares, Karina Kroll
dc.creatorSilvério, Jaline Coutinho
dc.creatorSilva, Andrea Alice da
dc.creatorMichailowsky, Vladimir
dc.creatorMarino, Ana Paula
dc.creatorSilva, Neide Maria
dc.creatorCarvalho, Cristiano Marcelo Espinola
dc.creatorPinto, Luzia Maria de Oliveira
dc.creatorGazzinelli, Ricardo Tostes
dc.creatorVieira, Joseli Lannes
dc.date2013-07-04T18:08:54Z
dc.date2013-07-04T18:08:54Z
dc.date2008
dc.date.accessioned2023-09-26T23:25:48Z
dc.date.available2023-09-26T23:25:48Z
dc.identifierKROLL 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.identifierhttps://www.arca.fiocruz.br/handle/icict/6650
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8890481
dc.descriptionIn 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.formatapplication/pdf
dc.languageeng
dc.rightsopen access
dc.subjectheart disease
dc.subjectinflammation
dc.subjectTrypanosoma cruzi
dc.subjectCCR5
dc.subjectTNFR1
dc.subjectTNF-α
dc.titleTNF/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.typeArticle


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