Metabolic reprogramming of monocytes/macrophages by first trimester trophoblast derived factors

. F MERECH, S GORI, D PAPARINI, V HAUK, R RAMHORST, D VOTA, C PEREZ LEIROS.

virtual

Congreso; Reunión Anual Conjunta SAIC-SAI-SAFIS; 2021

Immune regulation during placentation is crucial for fetal growth. Loss of immune homeostasis at the maternal-fetal interface is as-sociated with preeclampsia and fetal growth restriction. A tight in-teraction 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 (CM) of Tb that contribute to CD14+ cell expression of an anti-inflammatory profile. Tb cells present high glycolysis rate with high lactate production which is known to induce tolerogenic and anti-inflammatory profiles in tumor-associated macrophages. Our aim is to evaluate the effect of Tb derived factors on CD14+ cell metabolic reprogramming, focusing on glucose and fatty acid metabolism. For CD14+ isolation, peripheral blood of healthy donors was pro-cessed by Ficoll-Paque/Percoll. Cells were cultured or not for 5 days with M-CSF. CM was collected from human first trimester Tro-phoblast-derived cell line Swan-71. Phenotypic marker expression, glucose uptake with D-glucose fluorescent analog (2-NBDG) and lipid droplets with Bodipy 493/503 were analyzed by flow cytometry. 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 (Mean±SEM): Basal 32.9 ± 4.1%; LPS 51.8 ± 8.5%; n=11). Tb CM prevented LPS-induced glucose uptake: CM-LPS 23.7 ± 4.5% (p