ANALYSING THE ROLE OF WNT SIGNALING IN M1 MACROPHAGE POLARIZATION

• Autores: Herrera, Melisa; Sofía Vallon Trabelsi; Juan Nahuel Quiroz; Brugo, María Belen; Volpini, Ximena; Claudia Motran
• Año de publicación: 2022
• Idioma: inglés
• Tipo de recurso: documento de conferencia
• Materia: MACROPHAGES; POLARIZATION; WNT
• Institución: Universidad Nacional de Córdoba

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<0.001) and IL-6 (p<0.05) than control cells. However, they showed higher phagocytic capacity (p<0.001) and higher secretion of IL-12 (p<0.01) and IL-1β (p<0.05) than vehicle-treated cells. As expected, the M1 stimulus increased the percentage of cells expressing the M1 markers CD86+ CD38+ (p<0.01), while did not induce Arg-1 expression. Interestingly, inhibition of Wnt signaling increased the percentage of Arg-1+ CD86- CD38- and Arg-1 + CD86+ CD38+ cell populations. Our results suggest that Wnt signaling participates in M1 polarization induced by classical stimulus by modulating the expression of key molecules that contribute to this phenotype.
Inmunología