TROPHOBLAST-MONOCYTE/MACROPHAGE INTERACTION ELICITS BIDIRECTIONAL METABOLIC REPROGRAMMING

MERECH, FÁTIMA; GORI, SOLEDAD; REYSCHER, GRACIELA; PAPARINI, DANIEL; HAUK, VANESA; VIDELA, MARIELA; GARCIA, MARIELA; RAMHORST, ROSANNA; MONGE, MARÍA; VOTA, DAIANA; PÉREZ LEIRÓS, CLAUDIA

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología y de la Sociedad Argentina de Investigaciones Clínicas; 2022

maintenance at placentation. Tb modulate decidual macrophages to an anti-inflammatory profile through cytokines and other factors released. Both Tb and macrophages display highly active metabolism to adapt to variable nutrient and oxygen placental microenvironments. However, a role for metabolites as mediators in the trophoblast-macrophage interaction is unclear, entailing a new research area within Immunometabolism sustained on novel metabolomics approaches. We have shown that the conditioned media of Tb (Tb-CM) prevent LPS-induced glucose uptake in monocytes/macrophages (CD14+) and promote anti-inflammatory markers. Here we studied the trophoblast-CD14+ cell metabolic rewiring upon in vitro interaction.Monocytes were isolated from peripheral blood of female donors by Percoll. M1 macrophages were obtained after differentiation 5+2 days with GM-CSF and E. coli LPS; M1 conditioned media (M1-CM) collected in RPMI-FBS 2% 24h later. Tb metabolism was studied in the human trophoblast cell line Swan71. Tb-CM was collected after 18h. Glucose, long chain polyunsaturated fatty acids (LCPUFAs) uptake and lipid droplets were evaluated using D-glucose analog (2-NBDG), Bodipy FL C12 or 493/503 respectively by flow cytometry, and gene expression by RT-qPCR. Proinflammatory M1-CM induced rapid (4h) glucose uptake in Tb and increased cell migration. However, it decreased TNFa and IL1b (p