Immunometabolic reprograming of neutrophils by trophoblast cells in an in vitro model of early maternal-placental interface.

G CALO, D VOTA, F SABBIONE, F MERECH, V HAUK, R RAMHORST, A TREVANI AND C PÉREZ LEIROS.

Congreso; Reunión Anual Conjunta SAIC-SAI-SAFIS; 2022

Trophoblast cells (Tb) interact with maternal immune cells at placentation favoring an anti-inflammatory microenvironment requiredfor fetal growth. We have previously shown that conditioned media from Tb cells (CM) induced a proangiogenic functional profileon neutrophils (PMN) but their immunometabolic reprogrammingin the context of pregnancy was not yet studied. The aim of thiswork was to evaluate the effect of trophoblast cell-derived factorsin neutrophils’ metabolic, phenotypic, and functional profile. PMNfrom healthy donors were cultured with human first trimester trophoblast cell line Swan71 or HTR8 CM. PMN profiles were assessed byqPCR and flow cytometry. Glucose uptake, lipid accumulation, longchain polyunsaturated fatty acids uptake reactive oxygen species(ROS) production and apoptosis were determined by flow cytometry using 2-NBDG, BODIPY 493/503, FLC12, DCFH-DA or AnnexinV– Propidium Iodide respectively. PMN cultured with CM enhancedglucose uptake and lipid droplet (LD) accumulation although to alower extent than PMA. Also, an increase in the glucose specifictransporter GLUT1 and lactate dehydrogenase A was observed.Treatment with lactate -a metabolite greatly released by Tb- slightlyincreased ROS production (X±SE Basal 12152±1018 20mM lactate 16405±991, P