Maturation of cord blood natural killer (NK) cells differs among neonates

Abstract

Abstract The source, timing of colonization, and stability of the neonatal microbiome is largely unknown. We and other groups recently demonstrated that infant colonization may begin in utero, challenging the notion that neonates are born sterile. However, neonates are particularly vulnerable to viral infection partially due to dampened responses from NK cells and delayed maturation of adaptive immunity. Given the degree of variability in neonatal vulnerability to infection, we hypothesized that intrauterine exposure to microbes enables a greater diversity of NK cells in the neonates, relative to the adult, to allow for immune tolerance. Here, we performed multi-parametric flow cytometry analyses to dissect the normal range and expression of human NK cell developmental markers from umbilical cord (UC) blood (n=37). NK cells were identified as CD45+ CD3− CD56+ using FlowJo X and Cytobank. UC blood had a lower frequency of mature NK cells than adult peripheral blood. Furthermore, examination of NK cell maturation via spanning analysis of density events (SPADE) highlighted inter-individual diversity of neonatal NK cell subsets. Diversity of NK cells subsets between neonates and adults was significantly different with higher diversity in neonates (Simpson’s Diversity Index, p = 0.008). Our findings suggest diversity in stages of NK cell development between individual neonates that may reflect early immune exposure. Given ours and others recent work demonstrating that the intrauterine environment is not sterile, we speculate that microbial exposures during gestation may be a driving difference in the diversification NK cell populations in human infants and hence enable immune tolerance at the risk of neonatal viral vulnerability.