PD-1 and arginase activity in canine visceral leishmaniasis

Abstract

Visceral Leishmaniasis (VL) is a chronic and often fatal if untreated and is expanding in the state of São Paulo, in regions with urban characteristics as Araçatuba. According to the Secretary of Epidemiological Surveillance State of São Paulo, the disease is expanding with a high mortality rate, and the Araçatuba region has the largest number of cases in the state. The canine VL is a serious public health problem because infected animals are powerful transmitters of the parasite to humans through the vector, and canine disease is more prevalent than the human disease, canine cases usually precede human cases. The dog is therefore a major target in control measures. The progression of canine infection is accompanied by failure in cellular immunity with reduced circulating lymphocytes and the production of cytokines that suppress microbicidal function of macrophages, suppression of T cells is well documented, but the mechanisms that lead to failure in the immune response are little known. Recently the involvement of the receptor PD-1 costimulatory negative in adaptive responses in chronic infectious diseases has been reported. When this receptor is present in immune cells bound to its counter-receptor PD-L1 or PD-L2 triggers inhibitory signals that lead to T cell deactivating; another important regulator of immune responses is arginase 1, the activity of this enzyme appears to interfere negatively in T cell effector function. Both receptor PD1 as arginase activity act together regulating immune responses, but no studies have evaluated whether suppression of cellular response in dogs with visceral leishmaniasis is related to these molecules. The proposal of this study is investigate on the dogs naturally infected if the failure of cellular immunity and increased parasite load may be due to the expression of costimulatory negative molecules and increased of arginase 1 in the spleen. For this expression of PD1 and their ligands will be evaluated together with the activity of the enzyme arginase 1 and will be quantified parasite burden. Knowledge of this study may be useful in the design of immunotherapeutic drugs (AU)