MONOCYTE/MACROPHAGE METABOLIC REPROGRAMMING IN A MODEL OF MATERNAL-PLACENTAL INTERACTION

F MERECH; S GORI; G REYSCHER ; D PAPARINI; V HAUK; R RAMHORST; D VOTA; C PÉREZ LEIRÓS

Congreso; IMMUNOMETABOLISM MEETING, 46 SBI CONGRESS; 2022

Introduction: A finely modulated interaction between maternal leukocytes and trophoblast cells is critical for normal pregnancy and fetal growth. Loss of immune homeostasis at the maternal-fetal interface is associated with pregnancy complications as preeclampsia and fetal growth restriction.Monocytes recruited to the placenta from early stages and decidual macrophages activated in an M2 alternative profile contribute to immunotolerance at placentation. Trophoblast cells (Tb) promote M2 macrophages as shown using human trophoblast conditioned media and mouse models. Evidence that tumor, neural and infectious microenvironment induce metabolic changes in macrophages accumulates but the mechanisms of macrophage immunometabolic rewiring by trophoblast cells and its impact in pregnancy outcome is still unclear.Objective:Our aim is to evaluate the effect of Tb-derived factors on the metabolic reprogramming of CD14+ cells. Methods and Results:Monocytes were isolated from peripheral blood of healthy female donors by Ficoll-Paque/Percoll and cultured or not with M-CSF for 5 days. Tb conditioned media (Tb-CM) was obtained from human cytotrophoblast cell line Swan-71 cultures. CD14+ cell phenotype was analyzed by flow cytometry. Glucose uptake, long chain polyunsaturated fatty acids (LCPUFAs) uptake and neutral cytoplasmic lipid droplets were determined by flow cytometry using D-glucose fluorescent analog (2-NBDG), Bodipy FL C12 and Bodipy493/503, respectively. Lactate production was quantified with Accutrend Plus.Tb-CM increased LCPUFAs uptake in CD14+ cells upon 20 min and 18 h stimulation (p