Alkaloids from Galipea longiflora Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4⁺ T cells

Alkaloids obtained from the plant Evanta have been shown to have dual effects in Leishmania infection; a direct leishmanicidal effect on the parasite and more importantly, the alkaloids affect both polyclonal and Leishmania-specific stimulation of T-cells. Dendritic cells (DCs) play a pivotal role in stimulation and polarization of naïve T cells towards a Th1, Th2, Th17 or regulatory phenotype. In leishmaniasis, the interactions between the parasites and DCs are complex and involve contradictory functions that can stimulate or suppress T cell responses, leading to the control of infection or progression of disease. In this study the effect of an alkaloid extract of Evanta (AEE) or the purified alkaloid 2-phenilquinoline (2Ph) on the activation of human DCs and their ability to stimulate allogeneic CD4⁺ T cells was analyzed. The expression of surface activation molecules was not affected on DCs stimulated in the presence of AEE or 2Ph nor did AEE-DCs or 2Ph-CDs affect the expression of activation surface molecules on allogeneic CD4⁺ T cells. In contrast, as compared with control, the secretion of IL-12p40, IL-23 and IL-6 was lower from AEE-DCs and 2Ph-CDs and allogeneic CD4⁺ T cells co-cultured with these DCs secreted lower levels of IFN-γ and IL-10 but the same levels of IL-17. These results demonstrate that AEE and 2Ph affect the stimulation of DCs and their ability to stimulate allogeneic CD4⁺ T cells by reducing the production of IFN-γ, IL-12 p40, IL-6 and IL-23. This suggests that AEE and 2Ph may take part in regulation of inflammation.