CCL2 stimulation drives rapid postnatal changes in the immune-metabolic phenotype of neonatal monocytes

Birth is a profound physiological and immunological transition, during which the newborn must rapidly adapt to a microbe-rich environment. In contrast to adults, neonates allocate substantial energy toward body growth, which in turn influences their antimicrobial defenses. Using systematic analysis of immunometabolism, RNA expression and plasma kinase activity in human cord blood, peripheral neonatal blood, and adult blood, we uncovered rapid postnatal metabolic changes, which were confirmed in mice. Immune cells from neonates exhibit a marked increase in metabolic activity immediately after birth, characterized by elevated glycolytic flux and enhanced mitochondrial function. We further demonstrate an activation of the CCL2-CCR2 signaling axis as a critical mechanism mobilizing metabolically active monocytes from the bone marrow to the circulation. This specific monocytic immune-metabolic phenotype is related to mode of delivery and not to early microbial exposure as demonstrated in gnotobiotic mice. Collectively, our study demonstrates rapid immune-metabolic adaptations, comparable to emergency hematopoiesis, that drive postnatal immune development during the first days of life.