EFFECT OF METFORMIN TREATMENT ON THE EXPRESSION OF COSTIMULATORY AND INHIBITORY MOLECULES IN PERITONEAL AND SPLEEN MACROPHAGES OF TRYPANOSOMA CRUZI INFECTED MICE.

BAIGORRÍ, RUTH ELIANA; MARÍA FLORENCIA HELLRIEGEL; BRUGO MARIA BELEN; MATIAS VAZQUEZ; VIANO, MARIA ESTEFANIA; RODRIGUEZ-GALAN, MARIA CECILIA; CRISTINA MOTRAN; STEMPIN, CINTHIA CAROLINA; CERBAN, FABIO

Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2022

Macrophages (Mφ) are antigen presenting cells (APC) that interactwith primed CD4 T cells. This interaction is supported by surfaceand soluble mediators that promote a cellular or humoral response.Previously, we demonstrated in our in vivo model that peritoneal Mφ(PEM) and F4/80+CD11b+ spleen Mφ (SpM) exhibit high iNOS expressionand NO release in the acute phase that could be revertedby Metformin (MF) treatment. MF is a diabetes drug that can modulateseveral pathways switching Mφ phenotype and function. In orderto characterize the APC features of PEM and SpM we infectedBalb/c mice i.p. with 500 trypomastigotes. At different times of infectionwe analyzed CD80, CD86, PD-L1 and PD-L2 expression byflow cytometry. We found an increase in CD80 and PD-L1 and lessCD86 and PD-L2 positive cells in SpM in 23 dpi. PEM also increasethe percentage of both CD80+ and PD-L1+ cells. Then, to evaluatewhether MF treatment of PEM could modulate costimulatory andinhibitory molecules and impact T cell activation, we cocultured totalstimulated-splenocytes with infected PEM treated ex vivo with PBSor MF. We found a non-significant decrease in CD4 T cell proliferationassessed by CFSE dilution when splenocytes were coculturedwith infected PEM. This effect was even higher in cocultures withinfected and MF treated-PEM. Afterward, we evaluated expressionof these molecules in an in vivo oral MF treatment of infected Balb/c mice (100 mg/kg beginning at day 6 until 18 dpi). We did notobserve differences in PD-L1 expression of PEM or SpM. However,both populations of Mφ showed a clear tendency to decreasein CD80 expression. In addition, we analyzed PD-1 expression inTreg, Tconv and CD8 T cells. Although MF treatment did not modifyPD-1 expression in these cells we found an decrease in Treg cellsin infected and MF treated animals compared with controls. Theseresults suggest a potential role of Mφ in T cell activation that couldbe modulated by MF during T. cruzi infection.