Effect of Metformin treatment on the expression. Of coestimulatory and inhibitory molecules in peritoneal and spleen macrophages of Trypanosoma cruzi infected mice.

BAIGORRI, RE, HELLRIEGEL MF, BRUGO MB, VÁZQUEZ VIGNALE ME, VIANO ME, RODRÍGUEZ MC, MOTRÁN, CC, STEMPIN CC, CERBÁN FM.

Mar del Plata

Congreso; Reunión de Sociedades de Biociencias 2022 - LXX Reunion Anual de la Sociedad Argentina de Imunologia.; 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 the percentage of both CD80+ and PD-L1+ cells. Then, to evaluate 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 PBS or 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.