| Texto completo | |
| Autor(es): |
Pontes Ferreira, Camila
[1]
;
Moro Cariste, Leonardo de
[2]
;
Henrique Noronha, Isau
[1]
;
Fernandes Durso, Danielle
[3]
;
Lannes-Vieira, Joseli
[4]
;
Ramalho Bortoluci, Karina
[5]
;
Araki Ribeiro, Daniel
[2]
;
Golenbock, Douglas
[3]
;
Gazzinelli, Ricardo Tostes
[3]
;
Vasconcelos, Jose Ronnie Carvalho de
[2, 1]
Número total de Autores: 10
|
| Afiliação do(s) autor(es): | [1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biosci, Santos, SP - Brazil
[3] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA - USA
[4] Fiocruz MS, Lab Biol Interact, Inst Oswaldo Cruz, Rio De Janeiro - Brazil
[5] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PLoS Neglected Tropical Diseases; v. 14, n. 6 JUN 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
Chemokine receptor type 3 (CXCR3) plays an important role in CD8(+)T cells migration during intracellular infections, such asTrypanosoma cruzi. In addition to chemotaxis, CXCR3 receptor has been described as important to the interaction between antigen-presenting cells and effector cells. We hypothesized that CXCR3 is fundamental toT.cruzi-specific CD8(+)T cell activation, migration and effector function. Anti-CXCR3 neutralizing antibody administration to acutelyT.cruzi-infected mice decreased the number of specific CD8(+)T cells in the spleen, and those cells had impaired in activation and cytokine production but unaltered proliferative response. In addition, anti-CXCR3-treated mice showed decreased frequency of CD8(+)T cells in the heart and numbers of plasmacytoid dendritic cells in spleen and lymph node. As CD8(+)T cells interacted with plasmacytoid dendritic cells during infection byT.cruzi, we suggest that anti-CXCR3 treatment lowers the quantity of plasmacytoid dendritic cells, which may contribute to impair the prime of CD8(+)T cells. Understanding which molecules and mechanisms guide CD8(+)T cell activation and migration might be a key to vaccine development against Chagas disease as those cells play an important role inT.cruziinfection control. Author summary Inflammatory chemokine receptors such as CXCR3 play an important role in T lymphocytes migration into an infected tissue during Th1 response. Recently, the role of CXCR3 as a co-stimulatory molecule was demonstrated, and T lymphocytes from CXCR3 deficient mice had impaired effector function. CXCR3 receptor was highly expressed on specific CD8(+)T cells after challenge withT.cruzi, and the hypothesis of that molecule is important for CD8(+)T cells activation, migration and functionality was raised. We used the anti-CXCR3 neutralizing antibody approach and demonstrated that C57BL/6 treated mice died very quickly due toT.cruziinfection, and specific CD8(+)T cells had decreased effector phenotyping, cytokine production, and cytotoxicity. In addition, anti-CXCR3 treatment decreased the number of dendritic plasmacytoid cells in the lymphoid tissues. The lower quantity of dendritic plasmacytoid cells in those tissues might contribute to the decrease in CD8(+)T cells activation. Overall, CXCR3 molecule seems to be an important molecule to be explored during vaccine against Chagas disease strategies. (AU) | |
| Processo FAPESP: | 18/15607-1 - Papel das células T CD4+ e T CD8+ específicas geradas por diferentes protocolos de vacinação contra infecção experimental pelo Trypanosoma cruzi |
| Beneficiário: | Jose Ronnie Carvalho de Vasconcelos |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2 |
| Processo FAPESP: | 15/08814-2 - Papel de integrinas e receptores de quimiocinas na migração de células T CD8+ específicas geradas pela imunização genética com ASP-2 de Trypanosoma cruzi |
| Beneficiário: | Camila Pontes Ferreira |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 19/17994-5 - Papel do receptor de quimiocina CX3CR1 e da integrina LFA-1 na diferenciação e ativação de linfócitos T CD8 durante a infecção pelo Trypanosoma cruzi |
| Beneficiário: | Leonardo Moro Cariste |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 16/02840-4 - Efeito do inibidor farmacológico de mTOR rapamicina na resposta de linfócitos T CD8+ de memória induzidos pela vacinação genética usando a estratégia de prime-boost heterólogo |
| Beneficiário: | Barbara Ferri Moraschi |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |