Role of heme oxygenase 1 in canine visceral leishmaniasis

Abstract

Visceral Leishmaniasis (VL) is a chronic and often fatal disease if untreated in humans. It has expanded in the state of São Paulo, in regions with urban characteristics such as Araçatuba. According to the Secretary of Epidemiological Surveillance of São Paulo State, the disease is expanding with a high mortality rate, and the region of Araçatuba has the largest number of cases in the state. The canine VL is a serious public health problem because infected dogs are the greater transmitters of the parasite to humans through the vector, and considering that canine disease is more prevalent than the human disease and that the canine cases usually precede human´s. The dog is therefore a major target in control measures. The canine disease progression is accompanied by failure in cellular immunity and cytokine production that suppress the microbicidal function of macrophages, suppression of T cells is well documented, but the mechanisms that lead to failure in the immune response are poorly understood. Recently the involvement of heme oxygenase-1 (HO-1) in visceral leishmaniasis was reported; experimental model have shown that its expression modulates the immune response and appears to be involved in susceptibility to infection. In addition to its immunoregulatory function HO-1 is an enzyme that degrades heme, a pro-oxidant agent derived from hemoglobin released during the lysis of red blood cells therefore the enzyme acts as an antioxidant agent in the body. In canine visceral leishmaniasis oxidative metabolism is altered, suggesting the involvement of the enzyme in immune response, in addition, preliminary results showed a higher plasma concentration of the enzyme in infected dogs compared to healthy subjects. In order to assess the importance of HO-1 in the immune response of dogs with visceral leishmaniasis, will be used 10 control and 20 infected dogs, plasma and splenic levels of the enzyme will be evaluated and correlated with the presence of IL-10 in spleen and plasma oxidative stress markers, and substances associated with the metabolism of heme. In vitro assays will be performed to determine the effect of HO-1 on the Ag-specific lymphocyte proliferation, the rate of infection by Leishmania spp. macrophages in healthy as well as cytokine production under these conditions, spleen parasite burden will also be correlated with expression of the enzyme. Because of the importance of dogs in urban cycle of the disease, the understanding of the immunopathological mechanisms of disease can be useful to enhance control measures. (AU)