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; HELLRIEGEL, MARIA FLORENCIA; BRUGO, MARIA BELEN; VAZQUEZ, MATIAS; VIANO, MARIA ESTEFANIA; RODRIGUEZ-GALAN, MARIA CECILIA; MOTRÁN, CLAUDIA CRISTINA; STEMPIN, CINTHIA CAROLINA; CERBÁN, FABIO MARCELO

Mar del Plata

Congreso; Reunión anual de sociedades de biociencias SAIC. SAI. SAFIS; 2022

Macrophages (Mφ) are antigen presenting cells (APC) that interact with primed CD4 T cells. This interaction is supported by surface and 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 expression and NO release in the acute phase that could be reverted by Metformin (MF) treatment. MF is a diabetes drug that can modulate several pathways switching Mφ phenotype and function. In order to characterize the APC features of PEM and SpM we infected Balb/c mice i.p. with 500 trypomastigotes. At different times of infection we analyzed CD80, CD86, PD-L1 and PD-L2 expression by flow cytometry. We found an increase in CD80 and PD-L1 and less CD86 and PD-L2 positive cells in SpM in 23 dpi. PEM also increase whether MF treatment of PEM could modulate costimulatory and inhibitory molecules and impact T cell activation, we cocultured total stimulated-splenocytes with infected PEM treated ex vivo with PBSor MF. We found a non-significant decrease in CD4 T cell proliferation assessed by CFSE dilution when splenocytes were cocultured with infected PEM. This effect was even higher in cocultures with infected and MF treated-PEM. Afterward, we evaluated expression of 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 not observe differences in PD-L1 expression of PEM or SpM. However, both populations of Mφ showed a clear tendency to decrease in CD80 expression. In addition, we analyzed PD-1 expression in Treg, Tconv and CD8 T cells. Although MF treatment did not modify PD-1 expression in these cells we found an decrease in Treg cells in infected and MF treated animals compared with controls. These results suggest a potential role of Mφ in T cell activation that could be modulated by MF during T. cruzi infection.