METFORMIN TREATMENT MODULATES MACROPHAGE RESPONSE AGAINST T. CRUZI INFECTION.

BAIGORRÍ, RE; ANA, Y; BRUGO, MB; VIANO, ME; RODRIGUEZ GALAN, MC; MOTRAN, C; STEMPIN, C; CERBAN, F

Congreso; Reunión de Sociedades de Biociencias 2021 - LXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2021

In acute phase of T. cruzi infection, both innate and adaptive immunity are necessary to control parasite replication. Macrophage (Mf) and T cells orchestrate the inflammatory response that controls parasite burden. However, an exacerbated immune response results in tissue damage, mainly by ROS and RNS release. Metformin (Mf), a type 2 diabetes drug, reduces inflammation in models of aging and pollution. In our in vivo model of T. cruzi infection in Balb/c mice, we observed that peritoneal and spleen Mf increase iNOS expression during acute phase. Pretreatment of BMDM with Mf prevents intracellular parasite replication and promotes proinflammatory cytokine production. We also infected RAW cells and then were treated with 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 flow citometry (p<0.05). To determine the effect of Mf in T. cruzi infection, we infected i.p. mice with 500 trypomastigotes (tp) and then were treated 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) and PC, including control mice groups. Parasitaemia were assessed in both groups of infected mice showing less tp/mL in Mf treated mice (p<0.05). We found that both peritoneal infected Mf subsets, LPM and SPM increase mROS production (p<0.001) but Mf has no effect neither cROS/mROS production nor iNOS expression. Spleen Mf showed more iNOS+ cells in response to infection and Mf exhibited a slight revert. In LN, CD169+ Mf capture and prevent pathogens spread and initiate immune response driving B cell activation. We found a decrease in CD169+ Mf in infected mice that Mf could not restore. Surprisingly, these remaining cells showed more percentage of iNOS+ Mf (p<0.05). These results suggest that Mf could be apromising anti-inflammatory molecule to control tissue damage and modulate immune response to T. cruzi.