Louis M Weiss, Mahalia S Desruisseaux, Oscar B Akide-Ndunge, Jesmond Dalli, Michael Zingman, Shankar Mukherjee, Jyothi Nagajyothi, Herbert B Tanowitz, Jinet Reyes, Fabiane Matos Dos Santos, Anthony W Ashton, Linda A Jelicks, Fangxia Guan, Charles N Serhan, Romain A Colas, Huan Huang
Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD). CD is a persistent, life-long infection affecting many organs, most notably the heart where it may result in acute myocarditis and chronic cardiomyopathy. The pathological features include myocardial inflammation and fibrosis. In the Brazil-strain infected CD-1 mouse that recapitulates many of the features of human infection, we found increased plasma levels of resolvin D1 (RvD1), a specialized pro-resolving mediator of inflammation, both during the acute and chronic phases of the infection (>100 days post infection) as determined by ELISA. Additionally, ELISA on lysates of trypomastigotes of both the Tuliahan and Brazil strains revealed elevated levels of RvD1 when compared with lysates of cultured epimastigotes of T. cruzi, tachyzoites of Toxoplasma gondii, and trypomastigotes of T. brucei, cultured L6E9 myoblasts and culture media containing no cells. Lysates of T. cruzi --infected myoblasts also displayed increased levels of RvD1. Lipid mediator metabolomics confirmed that the trypomastigotes of T. cruzi produced RvD1, RvD5 and RvE2, which have been demonstrated to modulate the host response to bacterial infections. Plasma levels of RvD1 maybe both host and parasite derived. Since T. cruzi synthesizes specialized pro-resolving mediators of inflammation as well as pro-inflammatory eicosanoids, such as thromboxane A2, one may speculate that by using these lipid mediators to modulate its microenvironment, the parasite is able to survive.