Modified lipids from Trypanosoma cruzi amastigotes down-regulate the pro-inflammatory response and increase the expression of alternative activation markers in macrophages.

Herein, we analyzed the in vitro effect induced by total lipid extracts from Trypanosoma cruzi amastigotes of RA and K98 strains, which were obtained after overnight incubation (RAinc and K98inc) to mimic phospholipid hydrolytic processes that occurred adjacent to degenerating amastigote nests in tissues of Chagas disease patients. We demonstrated that RAinc and K98inc might possess bioactive lipid molecules with anti-inflammatory bias since they inactivated the NF-κB pathway, in contrast to intact lipids. Moreover, different M1/M2 macrophage phenotype markers of polarization were analyzed by RT-qPCR which evidenced that RAinc and K98inc promoted an increased expression of the M2 markers Arginase-1, IL-10, FIZZ and YM-1, and a decreased expression of iNOS and proinflammatory cytokines IL-6 and TNF-α. All these results indicate the relevant role of T. cruzi in bioactive lipid molecules, deepening thus our understanding of their contribution to immunomodulatory mechanisms as well as to macrophage polarization that occurs during the course of Chagas disease.