Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor

Autor(es):Mostrar menos -

Gutierrez, Fredy R. S. ^[1] ; Mariano, Flavia S. ^[1] ; Oliveira, Carlo J. F. ^[1] ; Pavanelli, Wander R. ^[1] ; Guedes, Paulo M. M. ^[1] ; Silva, Grace K. ^[1] ; Campanelli, Ana P. ^[2] ; Milanezi, Cristiane M. ^[1] ; Azuma, Miyuki ^[3] ; Honjo, Tasuku ^[4] ; Teixeira, Mauro M. ^[5] ; Aliberti, Julio C. S. ^{[6, 7]} ; Silva, Joao S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem & Immunol, BR-14049900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Biol Sci, Bauru Dent Sch, Sao Paulo - Brazil

^[3] Tokyo Med & Dent Univ, Dept Mol Immunol, Grad Sch, Tokyo - Japan

^[4] Kyoto Univ, Dept Med Chem, Grad Sch Med, Kyoto - Japan

^[5] Univ Fed Minas Gerais, Dept Biochem & Immunol, Inst Biol Sci, Belo Horizonte, MG - Brazil

^[6] Cincinnati Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH - USA

^[7] Cincinnati Childrens Hosp, Med Ctr, Div Pulm Med, Cincinnati, OH - USA

• Tipo de documento: Artigo Científico
• Fonte: Infection and Immunity; v. 79, n. 5, p. 1873-1881, MAY 2011.
• Citações Web of Science: 29

Resumo

Trypanosoma cruzi infection causes intense myocarditis, leading to cardiomyopathy and severe cardiac dysfunction. Protective adaptive immunity depends on balanced signaling through a T cell receptor and coreceptors expressed on the T cell surface. Such coreceptors can trigger stimulatory or inhibitory signals after binding to their ligands in antigen-presenting cells (APC). T. cruzi modulates the expression of coreceptors in lymphocytes after infection. Deregulated inflammation may be due to unbalanced expression of these molecules. Programmed death cell receptor 1 (PD-1) is a negative T cell coreceptor that has been associated with T cell anergy or exhaustion and persistent intracellular infections. We aimed to study the role of PD-1 during T. cruzi-induced acute myocarditis in mice. Cytometry assays showed that PD-1 and its ligands are strongly upregulated in lymphocytes and APC in response to T. cruzi infection in vivo and in vitro. Lymphocytes infiltrating the myocardium exhibited high levels of expression of these molecules. An increased cardiac inflammatory response was found in mice treated with blocking antibodies against PD-1, PD-L1, and to a lesser extent, PD-L2, compared to that found in mice treated with rat IgG. Similar results in PD-1(-/-) mice were obtained. Moreover, the PD-1 blockade/deficiency led to reduced parasitemia and tissue parasitism but increased mortality. These results suggest the participation of a PD-1 signaling pathway in the control of acute myocarditis induced by T. cruzi and provide additional insight into the regulatory mechanisms in the pathogenesis of Chagas' disease. (AU)

• Processo FAPESP: 04/05285-4 - Modulacao da resposta imune por celulas t regulatorias na infeccao por trypanosoma cruzi.
• Beneficiário: Flávia Sammartino Mariano Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 07/53940-0 - Células T reguladoras e TH 17 no controle da imunidade contra infecções, tumores e doenças autoimunes
• Beneficiário: João Santana da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 05/60762-5 - Papel de PD-1 (programmed cell death receptor 1) na infecção experimental por Trypanosoma cruzi
• Beneficiário: Fredy Roberto Salazar Gutierrez
• Modalidade de apoio: Bolsas no Brasil - Doutorado