Pregnancy Entails a Metabolic Rewiring of Maternal Circulating Neutrophils

CALO, GUILLERMINA; MERECH, FÁTIMA; SABBIONE, FLORENCIA; HAUK, VANESA; LARA, BRENDA; DOGA, LUCIANA; D'ERAMO, LUCIANA; SQUASSI, ALDO; RAMHORST, ROSANNA; TREVANI, ANALÍA; VOTA, DAIANA; LEIRÓS, CLAUDIA PÉREZ

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2024

0021-9541

Immunometabolism is an emerging growing field that focuses on the role of cellular metabolism in the regulation of immunecell function and fate. Thus, proliferation, differentiation, activation, and function of immune cell populations are modulated byreprogramming their fueling and metabolic pathways. Pregnancy entails a fine immune and metabolic regulation of thematernal−fetal interaction to assist the energetic demands of the fetus where trophoblast cells have a central role. Maternalneutrophil functional shaping by trophoblast cells has been proposed though their metabolic conditioning during pregnancyhas not been studied yet. Here, we explored the effects of trophoblast‐derived factors on the metabolic rewiring of neutrophilsfrom nonpregnant women and its impact on central functions like reactive oxygen species (ROS) production, neutrophilextracellular trap (NET) release, and migration. In parallel, the immunometabolic status and function of neutrophilsisolated from pregnant women (16−20 weeks) was compared with nonpregnant age‐matched control samples. Trophoblast‐derived factors induced glucose uptake and lipid droplet accumulation without activating ROS production or NET release.Conditioned media from trophoblast cells also inhibited PMA‐induced NETosis partly by impairing glucose uptake inneutrophils. In turn, neutrophils from pregnant women had increased basal ROS production, lipid accumulation, and glucoseuptake compared to neutrophils from nonpregnant women, accompanied by a higher release of PMA‐induced NETs. Interestingly, PMA‐induced NETs was blocked by a fatty acid oxidation inhibitor in neutrophils from pregnant women indicating thecontribution of fatty acid metabolism to neutrophil activity during pregnancy. Results are consistent with immunometabolicmechanisms underlying the functional shaping of neutrophils during pregnancy and point out the contribution of trophoblast‐derived factors to their metabolic profiling. These findings provide novel immunometabolic clues to understand immunehomeostasis maintenance during pregnancy and raise the clinical potential of monitoring neutrophil metabolism during normaland complicated pregnancies