CXCR3 chemokine receptor contributes to specific CD8(+) T cell activation by pDC during infection with intracellular pathogens

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]}

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

• 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