ANALYSING THE ROLE OF WNT SIGNALING IN M1 MACROPHAGE POLARIZATION

HERRERA, MELISA; SOFÍA VALLON TRABELSI; JUAN NAHUEL QUIROZ; BRUGO, MARÍA BELEN; VOLPINI, XIMENA; CLAUDIA MOTRAN

Mar del Plata

Congreso; Reunión anual de Sociedades de Biociencias; 2022

SAI-SAIC-FAIC

Wnt signaling pathways, in addition to participating in key cellular processes during organogenesis, plays an important regulatory role in infectious and inflammatory processes. The expression of Wnt proteins and the activation of the Wnt/β-catenin and Wnt/Ca++ pathways are induced in macrophages (Mo) infected with T. cruzi through TLR signaling. Notably, when both Wnt/-catenin pathway or the secretion of Wnt proteins are blocked using IWP-L6, the activity of arginase-1 (Arg-1) is inhibited, and Tc-infected Mo adopts an M1-like phenotype. Our hypothesis is that the activation of Wnt signaling pathways in Mo would play a critical role in defining the activation/polarization profile of these cells after activation by TLR ligands. Thus, to investigate the role of Wnt signaling pathways in Mo polarization to M1, J774 cells or bone marrow derived Mo were treated with IWP-L6 or vehicle for 24 h and then stimulated with IFN-γ plus LPS (M1 stimulus). The production of NO, IL-6, IL-12 and IL-1β was evaluated in culture supernatant and the expression of CD86, CD38 and Arg-1 determined by FACS at 48 h post stimulation. In addition, phagocytosis assay of heat-killed Candida albicans was assessed using light microscopy. Cells treated with IWP-L6 before the M1-polarizing stimulus showed a lower production of NO (p