METFORMIN REGULATES INFLAMMATORY RESPONSE OF T. CRUZI-INFECTED PERITONEAL MACROPHAGES IN AN EX VIVO TREATMENT MODEL.

BAIGORRÍ, RUTH ELIANA; ANA, YAMILE; BRUGO MARIA BELEN; VOLPINI, XIMENA; CRISTINA MOTRAN; CINTHIA STEMPIN; CERBAN, FABIO MARCELO

Congreso; Reunión de la Sociedad Argentina de Inmunología; 2020

During the acute phase of T. cruzi infection, high replication of theparasite is controlled by a strong inflammatory response with activationof the innate immune cells due to increase of Th1 proinflammatorycytokines. Macrophages (Mø) have been described to controlintracellular parasite replication when iNOS expression and ON productionare induced in vitro. We previously reported that pretreatmentof bone marrow derived Mø with Metformin (Metf) leads thesecells to control parasite replication presumably by modulating inflammasomeactivation without increase of iNOS expression. However,it has been demonstrated that high and continuous ON release byMø and other cells, is involved in Th1 T cell suppression. In this context,Metf was associated to reduce inflammatory-related ischemiccardiovascular events, prolong lifespan and decrease aged-relatedinflammation. To determine the Mø activation profile during in vivo T.cruzi infection and the possibles effects of Metf treatment, we testediNOS expression by FACS in Peritoneal Mø (Pe-Mø) subsets, LPM(Large Pe-Mø) and SPM (Small Pe-Mø). We observed increasediNOS expression (p<0.001) in LPM and SPM during the acute phase(day 20 post infection) that declines around day 40, despite the highON levels in plasma at this point. To determine other sources of ONproduction we assessed iNOS expression in spleen cells by FACSand we found small but consistent F4/80+CD11b+iNOS+ cells. Afterthat, we performed an ex vivo treatment of total Pe-Mø from infectedmice in acute phase and we observed a decrease in supernatantslevels of ON and TNF-a levels by ELISA (p<0,05) when cells areexposed to Metf. To test if Metf polarize Mø to an antiinflammatoryprofile, we tested arginase expression by WB and IL-10 productionby ELISA but we observe no changes in these parameters. Takentogether, these results suggest that Metf could modulate exacerbatedMø activation during high parasitaemia acute phase that couldlead to organ damage.