METFORMIN TREATMENT MODULATES MACROPHAGE RESPONSE AGAINST T. CRUZI INFECTION

BAIGORRI RUTH; ANA, YAMILE; BRUGO, MARÍA BELÉN; VIANO, MARÍA ESTEFANÍA; RODRÍGUEZ-GALÁN, MA. CECILIA; MOTRÁN, CRISTINA; STEMPIN CINTHIA; CERBÁN FABIO

Congreso; Reunión de Biociencias 2021; 2021

In acute phase of T. cruzi infection, both innate and adaptive immunityare necessary to control parasite replication. Macrophage (Mf)and T cells orchestrate the inflammatory response that controls parasiteburden. However, an exacerbated immune response results intissue damage, mainly by ROS and RNS release. Metformin (Mf), atype 2 diabetes drug, reduces inflammation in models of aging andpollution. In our in vivo model of T. cruzi infection in Balb/c mice,we observed that peritoneal and spleen Mf increase iNOS expressionduring acute phase. Pretreatment of BMDM with Mf preventsintracellular parasite replication and promotes proinflammatory cytokineproduction. We also infected RAW cells and then were treatedwith PBS or Mf 1mM. This treatment decreased ROS production(p<0.05). Peritoneal cells (PC) of infected mice treated 48 h withMf reduce ROS production and iNOS expression assesed by flowcitometry (p<0.05). To determine the effect of Mf in T. cruzi infection,we infected i.p. mice with 500 trypomastigotes (tp) and then weretreated with PBS or 100 mg/kg of Mf daily by gavage. At 18 d.p.i.we obtained blood samples, spleen, inguinal lymph nodes (LN) andPC, including control mice groups. Parasitaemia were assessed inboth groups of infected mice showing less tp/mL in Mf treated mice(p<0.05). We found that both peritoneal infected Mf subsets, LPMand SPM increase mROS production (p<0.001) but Mf has no effectneither cROS/mROS production nor iNOS expression. Spleen Mfshowed more iNOS+ cells in response to infection and Mf exhibiteda slight revert. In LN, CD169+ Mf capture and prevent pathogensspread and initiate immune response driving B cell activation. Wefound a decrease in CD169+ Mf in infected mice that Mf could notrestore. Surprisingly, these remaining cells showed more percentageof iNOS+ Mf (p<0.05). These results suggest that Mf could be apromising anti-inflammatory molecule to control tissue damage andmodulate immune response to T. cruzi.