METABOLIC PROFILING OF MACROPHAGE VS DENDRITIC CELL DIFFERENTIATION

DIAZ, FERNANDO ERRA; BLEICHMAR, LUCÍA; MAZZITELLI, IGNACIO; MELUCCI GANZARAIN, CLAUDIA; GEFFNER, JORGE

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI & FAIC SAFIS 2022; 2021

Monocytes are highly plastic cells and can differentiate into macrophages (Mo-Macs) or dendritic cells (Mo-DCs). However, the environmental signals and the mechanisms that skew monocyte fate are poorly understood. While the cytokine GM-CSF induces mono- cyte differentiation into MoMacs, the combination of GM-CSF + IL-4 is the canonical way to generate MoDCs. Based on our previous findings indicating that mTORC1 inhibition in human monocytes promotes Mo-DC differentiation, we hypothesized that monocyte differentiation into either Mo-Macs or Mo-DCs could be associated with differential nutrient utilization and biased metabolic activity. To gain insight into the metabolic changes associated with these processes, we performed untargeted metabolomics (HPLC/MS) of cell culture supernatants (after 6 days of culture) of human mono- cytes undergoing Mo-Mac or Mo-DC differentiation in vitro (n=6). Differentiation of Mo-Macs was induced by GM-CSF (50ng/ml) (GM-MoMacs) while Mo-DC differentiation was induced by GM-CSF and IL-4 (30ng/ml) (GMIL4-MoDCs) or GM-CSF and Temsirolimus (50nM) (GMT-MoDCs). We detected 385 metabolites, 97 of which were differentially abundant among comparisons (p