Parasitic load determination by differential expressions of 5-lipoxygenase and PGE2 synthases in visceral leishmaniasis

In this study, we intend to explore linkage between organ specific immune response and eicosanoids. We suggest that eicosanoids (early immune modulators) and their organ specific expressions, possibly tune the outcome of mφ differently at different sites. We have observed that liver showed better containment of parasitic load than spleen, where we have found higher expression of 5-lipoxygenase (5-LO) enzyme along with IL-12 and iNOS. However, in spleen, enzymes of the PGE2 pathway i.e. PGE2 synthases (cytosolic and microsomal) along with IL-10 were predominantly higher. To further corroborate our findings, in vitro assays were carried out using purified eicosanoids (LTB4 and PGE2) and the inhibitors of these pathways. Findings establish that the 5-lipoxygenase pathway (i.e. LTB4) is anti-parasitic and its inhibition increases the parasitic load (qPCR based kDNA detection). On the contrary, PGES pathway (i.e. PGE2) supports establishment of infection in mφ. Taken together, 5-LO pathway plays a protective role in liver during L. donovani infection. However, the PGES pathway favors the parasite growth, particularly in the spleen at a later stage.Graphical abstract
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research