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Immune Signatures of Neonates
Abstract Number: T-80
Abstract Type: Original Research
Introduction: Neonatal immune systems have distinct cellular composition and functional capacity compared with the mature adult immune system. Both the innate and the developing adaptive immune systems are critical to infant health. However, the influence maternal immune traits have on neonatal systems is poorly understood. This study used mass cytometry to comprehensively map and interrogate the immune system of a cohort of neonates and their mothers (Gaudilliere, Sci Transl Med 2014) to test the hypothesis that specific functional responses in maternal immune cell lineages are associated with respective functional responses in sentinel neonatal innate and adaptive immune cell subsets.
Methods: Umbilical cord blood samples from neonates (n=11) and peripheral blood from their mothers (n=10), were stained with 21 cell surface and 15 intracellular functional markers (STAT1, STAT3, STAT5, STAT6, CREB, NFkB, IkB, p38, MAPK, MAPKAP2, ERK, S6, FoxP3, T-bet, GATA3) at basal state and after stimulation with exogenous ligands (LPS; IL-2, IL-10, GM-CSF, and INFa) that activate intracellular signaling networks implicated in innate and adaptive immune responses. Correlation network analysis was applied to identify immune features that significantly correlate between related mother and neonate pairs.
Results: Hierarchical clustering provided functional maps of the maternal and neonatal immune systems and revealed cell-type specific signaling responses to exogenous ligands. One representative example is shown in the figure. Importantly, with ligand stimulation, both response sensitivity and magnitude in specific immune cell subsets to biologically relevant “stressors” could be inferred.
Complete analysis, available at the time of the conference, will focus on: 1) the potential and feasibility of applying novel mass cytometry at the “bedside” to study immunity at the maternal/neonatal interface, and 2) immune traits that are uniquely shared between a mother and a neonate.
Conclusions: We present a comprehensive functional interrogation of the neonatal and maternal immune systems. These results may help predict morbidity and mortality associated with impaired immune function and will provide a unique description of the biology at the interface of maternal and neonatal immunity. These findings may be relevant to obstetric anesthesiologists as procedures, medications, and other interventions throughout pregnancy may impact the maternal/neonatal immune interface.