RESUMEN
PD-1 is a negative costimulator of chronic infectious diseases In this study, we investigated the expression of PD-1 and its ligands in the spleen of dogs with visceral leishmaniasis and lymphoproliferative response to soluble antigen, in lymph node cells in the presence or absence of antibodies blocking PD-1 and its ligands. Our results showed expression of PD-1 and its ligands is higher after L. infantum infection and in the spleen of infected dogs, PD-1 blockage was able to restore the antigen-dependent lymphoproliferative response and regulated production of the cytokines IL-4 and IL-10 and NO production. We concluded that L. infantum infection modulates PD-1 and its ligands expression in canine VL and that blockage of PD-1 restores the immune response. Thus, blockage of PD-1 is a target for therapeutic drug development.
Asunto(s)
Antígeno B7-H1/metabolismo , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/metabolismo , Inmunidad Celular , Leishmaniasis Visceral/veterinaria , Receptor de Muerte Celular Programada 1/metabolismo , Animales , Antígeno B7-H1/genética , Citocinas/metabolismo , Enfermedades de los Perros/parasitología , Perros , Femenino , Expresión Génica , Inmunohistoquímica , Inmunofenotipificación , Leucocitos/inmunología , Leucocitos/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Carga de Parásitos , Receptor de Muerte Celular Programada 1/genética , Bazo/inmunología , Bazo/metabolismoRESUMEN
Nitric oxide (NO) is involved in the death of the Leishmania parasite and regulation of apoptosis. We quantified the frequency of cells producing NO and its levels in the peripheral blood mononuclear cells (PBMC), leukocytes from spleen in Visceral Leishmaniasis (VL) symptomatic dogs and correlated NO levels with apoptosis and parasite load in the spleen. The percentage of NO+ cells and CD14+/NO+ was higher in PBMC and spleen cells in infected dogs than in controls. The levels of NO+ and CD14+/NO+ cells was higher in PBMC, but lower spleen of dogs infected than compared to control. Late apoptosis rates increased in PBMC and spleen of infected dogs compared to controls, and the NO levels and apoptosis not showed correlation. There was a positive correlation between the percentage of cells producing NO in the spleen and parasite load. The NO participates in the immune response in the canine VL, but it is not apoptosis inducer.