PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

Autor(es)

Chiku, Vanessa Marim ^[1] ; Oliveira Silva, Kathlenn Liezbeth ^[1] ; Martins de Almeida, Breno Fernando ^[1] ; Venturin, Gabriela Lovizutto ^[1] ; Correa Leal, Aline Aparecida ^[1] ; de Martini, Cleber Costa ^[1] ; Eugenio, Flavia de Rezende ^[2] ; Patto dos Santos, Paulo Sergio ^[2] ; Felix de Lima, Valeria Marcal ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, FMVA UNESP, Fac Vet Med Aracatuba, Rua Clovis Pestana 793, BR-16050680 Aracatuba, SP - Brazil

^[2] Univ Estadual Paulista, FMVA UNESP, Fac Vet Med Aracatuba, Dept Clin Care Surg & Anim Reprod, Lab Cellular Im, Rua Clovis Pestana 793, BR-16050680 Aracatuba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Immunobiology; v. 221, n. 8, p. 879-888, AUG 2016.
• Citações Web of Science: 14

Resumo

Dogs infected with Leishmania infantum have a reduced number of T lymphocytes. PD-1 (Programmed cell death 1) a new member of the B7-CD28 family that is expressed by immune cells, and its binding to PD-Ll (CD274) or PD-L2 (CD273) induces the deactivation or apoptosis of T cells. This study aimed to evaluate the expression of PD-1 and its ligands, as well as blocking in the induction of apoptosis in T lymphocytes, TNF-alpha, IL-4 and nitric oxide production by leucokocytes from PBMC and spleen and the parasite load in dogs with visceral leishmaniasis (VL). Our results showed that the expression of PD1 and its ligands was increased in CD3(+) T cells and CD21(+) B lymphocytes within the peripheral blood and splenic mononuclear cells of dogs with VL. In peripheral blood monocytes, only PD-1 ligands exhibited increased expression; however, in spleen macrophages, increased expression of both PD-1 and its ligands was observed. Levels of apoptosis in peripheral blood and splenic T lymphocytes were higher in dogs with VL compared to healthy dogs. Blocking monoclonal antibodies to PD-1 and its ligands in the culture of mononuclear cells from the peripheral blood and spleen decreased the amount of CD3(+) T lymphocyte apoptosis. The concentration of nitric oxide, TNF-alpha and IL-4 increased in the culture supernatants of peripheral blood mononuclear cells treated with a blocking monoclonal antibody against PD-1. The TNF-alpha concentration increased in the culture supernatants of splenic cells following all treatments with antibodies blocking PD-1 and its ligands; however, the amount of IL-4 increased only in the presence of a PD-1 blocking agent. Treatment with a PD-1 blocking monoclonal antibody in the mononuclear peripheral blood of dogs with VL reduced the parasite burden while increased TNF-alpha. We conclude that in canine visceral leishmaniasis, PD-1 and its ligands are involved in the induction of T lymphocyte apoptosis and in regulating the production of nitric oxide, TNF-alpha, and IL-4, as well as the parasitic load. (C) 2016 Elsevier GmbH. All rights reserved. (AU)

• Processo FAPESP: 13/19399-0 - Função de PD1 na apoptose de linfócitos T na leishmaniose visceral canina
• Beneficiário: Vanessa Marim Chiku
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/06684-9 - PD1, apoptose e atividade arginase na leishmaniose visceral canina
• Beneficiário: Valéria Marçal Felix de Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular