Potencial modulação do granuloma hepático pela proteína vegetal de Solanum tuberosum associada ao praziquantel subcurativo sobre a esquistossomose murina

Abstract

Schistosomiasis is an important neglected tropical disease caused by trematodes of the genus Shistossoma spp. It is an endemic parasite in more than 70 countries with approximately 230 million people affected and 800 million living in endemic areas. The disease is conditioned to populations of low socioeconomic status, where sanitation and sanitary education are deficient and is therefore a public health problem. Praziquantel (PZQ) is the current drug of choice, but it is not able to control the severe morbidity, which often affects patients. This bias invigorates the importance of controlling the morbidity and transmission of schistosomiasis. NTPDases are a family of proteins widely distributed among organisms, are enzymes that catalyze the hydrolysis of di and tri phosphate nucleotides. In Schistosoma mansoni, two isoforms were described SmATPase 1 and SmATPase 2. Potato aphidase (Solanum teberosum NTPDase) shows strong cross-immunoreactivity with partially purified S.mansoni isoforms, suggesting a sharing of conserved epitopes between parasite proteins and plant protein. We investigated the potential modulating effect of the plant protein associated with the PZQ subcurative on the pathogenesis of experimental schistosomiasis. The plant protein was purified by ammonium sulphate precipitation cycles, size change and ion exchange columns, the samples were lyophilized and the process efficiency confirmed by ATPase and ADPase enzymatic activity and SDS-page electrophoresis. Potato apyrase was employed in the immunogenicity assay in Balb/c mice (n=5) associated or not to sub-therapeutic praziquantel. The modulatory capacity of the plant protein on the immune system combined or not with the subcutaneous PZQ was evaluated in S.mansoni infected C57BL/6 (n=5) murine. The association between potato apyrase and PZQ induced the production of IgG, IgG1, IgG2a and IFN-γ in the experimental model of schistosomiasis mansoni and reduced the number of CD3+/CD4+, CD3+/CD8+ and cytokine IL-17 cells. Although potato apirase did not induce protection against schistosomiasis mansoni, it was able to reduce the diameter of hepatic granulomas. These data indicate that this protein can act in the modulation of granuloma by specific mechanisms, especially when associated with the PZQ subcurativo and to reduce the pathology caused by Schistosomiasis mansoni in murinos, thus being an important tool in the better understanding of the immunological mechanisms involved in the process and as a tool in the search for vaccine antigens and / or that are able to reduce the recurrent hepatic pathology in schistosomiasis