Involvement of lipids from Leishmania braziliensis promastigotes and amastigotes in macrophage activation

Abstract

Leishmania are obligate protozoan parasites responsible for substantial public health problems in tropical and subtropical regions around the world, with L. braziliensis being one of the causative agents of American Tegumentary Leishmaniasis. Macrophages, fundamental cells in the innate inflammatory response against Leishmania, constitute a heterogeneous group with multiple activation phenotypes and functions. The outcome of this infection depends largely on the activation status of macrophages, the first line of mammalian defense and the major target cells for parasite replication. The importance of lipids, the major components of cell membranes, goes beyond their basic structural functions. Lipid bioactive molecules have been described in Leishmania spp., and in the recent years the knowledge about the biological relevance of lipids in particular and their relationship with the immune response is expanding. The present work analyzes the biological effects of L. braziliensis lipids from lysed promastigotes (PRO) to mimic rapid modulatory processes that could occur in the initial steps of infection or the effects of lipids from lysed and incubated promastigotes (PROinc), simulating the parasite lipid degradation processes triggered after parasite lysis that might occur in the mammalian host. To perform these studies, lipid profiles of PRO and PROinc were compared with lipids from amastigotes under similar conditions (AMA and AMAinc), and the effect of these lipid extracts were analyzed on the induction of an inflammatory response in murine peritoneal macrophages: LB induction, COX-2, iNOS and Arginase expression, TNF-α, IL-10 and NO production, Arginase activity and M1/M2 markers mRNA induction.