METFORMIN TREATMENT MODULATES MACROPHAGE RESPONSE AGAINST T. CRUZI INFECTION

BAIGORRÍ, RUTH ELIANA; ANA, Y.; BRUGO MARIA BELEN; VIANO, MARIA ESTEFANIA; M CECILIA RODRIGUEZ GALAN; CRISTINA MOTRAN; CINTHIA STEMPIN; CERBAN, FABIO

Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2021

In the 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 with Th1 cells and production of pro inflammatory cytokines. However, an exacerbated immune response results in tissue damage, mainly by ROS and RNS release. It has been demonstrated that Metformin (Metf), the most used type 2 diabetes drug, reduces inflammation in models of aging and pollution. In our in vivo model of T. cruzi infection with Balb/c mice, we observed that peritoneal and spleen Mf increase iNOS expression during acute phase. We have previously reported that pretreatment of BMDM with Metf prevents intracellular parasite replication and promotes an inflammatory profile in these cells. To determine the effect of Metf against T. cruzi infection, we infected intraperitoneal Balb/c mice with 500 tripomastigotes (tp) and treated the animals with PBS or 100 mg/kg of Metf daily by gavage. At 18 d.p.i. we obtained blood samples, spleen, inguinal lymph nodes and peritoneal lavage including control mice groups. Parasitaemia were assessed in both groups of infected mice showing less tp/mL in Metf treated mice (p<0.01). Cell suspensions were analyzed by flow cytometry. We found that both peritoneal Mf subsets, LPM and SPM increase mROS production (p<0.001) but Metf has no effect neither cROS/mROS production nor iNOS expression. Spleen Mf showed more iNOS+ cells in response to infection and Metf exhibited a non-significative revert. In lymph nodes, 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 Metf could not restore. Surprisingly, these remaining cells showed more percentage of iNOS+ Mf (p<0.05). These results suggest that Metf could be a promising anti-inflammatory molecule to control tissue damage and modulate immune response to T. cruzi.