| Author | Nunes, Marise Pinheiro | |
| Author | Fortes, Bárbara | |
| Author | Silva Filho, João Luiz | |
| Author | Granado, Eugênia Terra | |
| Author | Santos, Leandro | |
| Author | Conde, Luciana | |
| Author | Oliveira, Isadora de Araújo | |
| Author | Lima, Leonardo Freire de | |
| Author | Martins, Marina Vieira | |
| Author | Pinheiro, Ana Acacia Sá | |
| Author | Takyia, Christina Maeda | |
| Author | Lima, Célio Geraldo Freire de | |
| Author | Todeschini, Adriane Regina | |
| Author | Reis, George Alexandre dos | |
| Author | Morrot, Alexandre | |
| Access date | 2015-10-02T12:45:04Z | |
| Available date | 2015-10-02T12:45:04Z | |
| Document date | 2013 | |
| Citation | NUNES.Marise Pinheiro.Inhibitory Effects of Trypanosoma cruzi Sialoglycoproteins on CD4+ T Cells Are Associated with Increased Susceptibility to Infection. Plos One, v.8, n.10, e77568, 13p, 2013. | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/11864 | |
| Language | eng | pt_BR |
| Publisher | Plos One | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Sialoglycoproteins | pt_BR |
| Subject in Portuguese | Infection | pt_BR |
| Subject in Portuguese | CD4+ T Cells | pt_BR |
| Title | Inhibitory Effects of Trypanosoma cruzi Sialoglycoproteins on CD4+ T Cells Are Associated with Increased Susceptibility to Infection | pt_BR |
| Type | Article | |
| DOI | 10.1371/journal.pone.0077568 | pt_BR |
| Abstract | Background: The Trypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens
characterized by decreased IL-2 synthesis. Trypanosoma cruzi mucin (Tc Muc) has been implicated in this phenomenom.
These molecules contain a unique type of glycosylation consisting of several sialylated O-glycans linked to the protein
backbone via N-acetylglucosamine residues.
Methodology/Principal Findings: In this study, we evaluated the ability of Tc Muc to modulate the activation of CD4+ T
cells. Our data show that cross-linking of CD3 on naı¨ve CD4+ T cells in the presence of Tc Muc resulted in the inhibition of
both cytokine secretion and proliferation. We further show that the sialylated O-Linked Glycan residues from tc mucin
potentiate the suppression of T cell response by inducing G1-phase cell cycle arrest associated with upregulation of
mitogen inhibitor p27kip1. These inhibitory effects cannot be reversed by the addition of exogenous IL-2, rendering CD4+ T
cells anergic when activated by TCR triggering. Additionally, in vivo administration of Tc Muc during T. cruzi infection
enhanced parasitemia and aggravated heart damage. Analysis of recall responses during infection showed lower
frequencies of IFN-c producing CD4+ T cells in the spleen of Tc Muc treated mice, compared to untreated controls.
Conclusions/Significance: Our results indicate that Tc Muc mediates inhibitory efects on CD4+ T expansion and cytokine
production, by blocking cell cycle progression in the G1 phase. We propose that the sialyl motif of Tc Muc is able to interact
with sialic acid-binding Ig-like lectins (Siglecs) on CD4+ T cells, which may allow the parasite to modulate the immune
system. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| DeCS | Trypanosoma cruzi | pt_BR |
| DeCS | Infecção | pt_BR |
| DeCS | Sialoglicoproteínas | pt_BR |
