METABOLIC REPROGRAMMING OF MONOCYTES/MACROPHAGES BY FIRST TRIMESTER TROPHOBLAST DERIVED FACTORS

MERECH, FATIMA; GORI, SOLEDAD; PAPARINI, DANIEL; HAUK, VANESA; RAMHORST, ROSANNA; VOTA, DAIANA; PÉREZ LEIRÓS, CLAUDIA

Congreso; Reunión Anual de Sociedades de Biociencias; 2021

Immune regulation during placentation is crucial for fetal growth. Loss of immune homeostasis at the maternal-fetal interface is associated with preeclampsia and fetal growth restriction. A tight interaction between trophoblast cells (Tb) and recruited monocytes and macrophages from early stages of pregnancy maintains an anti-inflammatory microenvironment. We have previously reported on soluble factors present in the conditioned media of Tb that contribute to CD14+ cell expression of anti-inflammatory and M2 markers. The vasoactive intestinal peptide (VIP) is among the Tb released factors that promote antiinflammatory responses and modulates Tb metabolism and function. On the other hand, Tb presents high glycolysis rate with a high lactate production, which is known to induce a tolerogenic and anti-inflammatory profile in tumor-associated macrophages. Our aim is to evaluate the effect of cytotrophoblast cells conditioned media on CD14+ cell metabolic reprogramming with special focus on glucose and fatty acid metabolism. For CD14+ cells isolation, peripheral blood of healthy donors was processed by Ficoll-Paque/Percoll before cultured or not for 5 days with M-CSF. Human cytotrophoblast cell line Swan-71 were cultured and conditioned media (CM) collected. Cytokine expression was analyzed by flow cytometry. Glucose uptake was measured using D-glucose fluorescent analog (2-NBDG), and lipid droplets were assessed by Bodipy 493/503, then flow cytometry was performed. Lactate production was quantified by Accutrend Plus system.Glucose uptake by CD14+ cells increased upon 20 min LPS (100 ng/ml) stimulation (% of CD14+ 2-NBDG high uptake cells (Mean±SEM): Basal 32.9 ± 4.1%; LPS 51.8 ± 8.5%; n=11). Trophoblast cell CM prevented LPS-induced glucose uptake: CM-LPS 23.7 ± 4.5% (p