METFORMIN TREATMENT MODULATES MACROPHAGE RESPONSE AGAINST T. CRUZI INFECTION

RUTH ELIANA BAIGORRÍ; YAMILE ANA; BELEN BRUGO; VIANO, MARIA ESTEFANIA; RODRIGUEZ-GALAN, MARIA CECILIA; CRISTINA MOTRÁN; CINTHIA STEMPIN; CERBÁN, FABIO

Congreso; REUNION CONJUNTA SAIC-SAI-AAFE-NANOMED; 2021

In acute phase of T. cruzi infection, both innate and adaptive immunity are necessary tocontrol parasite replication. Macrophage (Mf) and T cells orchestrate the inflammatoryresponse that controls parasite burden. However, an exacerbated immune responseresults in tissue damage, mainly by ROS and RNS release. Metformin (Mf), a type 2diabetes drug, reduces inflammation in models of aging and pollution. In our in vivomodel of T. cruzi infection in Balb/c mice, we observed that peritoneal and spleen Mfincrease iNOS expression during acute phase. Pretreatment of BMDM with Mf preventsintracellular parasite replication and promotes proinflammatory cytokine production.We also infected RAW cells and then were treated with PBS or Mf 1mM. This treatmentdecreased ROS production (p<0.05). Peritoneal cells (PC) of infected mice treated 48 hwith Mf 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 500trypomastigotes (tp) and then were treated with PBS or 100 mg/kg of Mf daily bygavage. At 18 d.p.i. we obtained blood samples, spleen, inguinal lymph nodes (LN) andPC, including control mice groups. Parasitaemia were assessed in both groups ofinfected mice showing less tp/mL in Mf treated mice (p<0.05). We found that bothperitoneal infected Mf subsets, LPM and SPM increase mROS production (p<0.001) butMf has no effect neither cROS/mROS production nor iNOS expression. Spleen Mfshowed 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 drivingB cell activation. We found a decrease in CD169+ Mf in infected mice that Mf could notrestore. Surprisingly, these remaining cells showed more percentage of iNOS+ Mf(p<0.05). These results suggest that Mf could be a promising anti-inflammatorymolecule to control tissue damage and modulate immune response to T. cruzi.