Stereotypic Immune System Development in Newborn Children

Abstract

SummaryEpidemiological data suggest that early life exposures are key determinants of immune-mediated disease later in life. Young children are also particularly susceptible to infections, warranting more analyses of immune system development early in life. Such analyses mostly have been performed in mouse models or human cord blood samples, but these cannot account for the complex environmental exposures influencing human newborns after birth. Here, we performed longitudinal analyses in 100 newborn children, sampled up to 4 times during their first 3 months of life. From 100 μL of blood, we analyze the development of 58 immune cell populations by mass cytometry and 267 plasma proteins by immunoassays, uncovering drastic changes not predictable from cord blood measurements but following a stereotypic pattern. Preterm and term children differ at birth but converge onto a shared trajectory, seemingly driven by microbial interactions and hampered by early gut bacterial dysbiosis.

Prenatal inflammation suppresses blood Th1 polarization and gene clusters related to cellular energy metabolism in preterm newborns

“…During the first week of life, both preterm and term infants show dramatic changes in systemic immune ontogeny with increased levels of gene expressions and proteins related to TLR signaling, neutrophil activity, and complement activation, as well as elevated Th1 and decreased Th2 polarization. 38,39 These tendencies of innate immune genes and Th2-related genes were very similar to changes on Day 5 vs at birth in both CON and LPS pigs in the current study, reflecting similarities in immune ontogeny in preterm pigs and preterm infants. Additionally, CON pigs also showed increased Th1 polarization with an elevated ratio of expressed TNFA/IL6, IFNG/IL4, IL12/IL4, and decreased the frequency of Treg over time, similar to newborn infants.…”

Gut microbiome interventions in human health and diseases

“…The same situation applies to infants treated with antibiotics . Moreover, systematic and longitudinal descriptions of immune cells and proteins in newborns show stereotypes of immune system development and its adaptation to intricate environmental exposure, among which perturbation of the gut microbiota leads to increased activated T cells in the blood . Babies born by cesarean section have a relatively simple gut microbiota with fewer species than do babies born naturally .…”

“…60 Moreover, systematic and longitudinal descriptions of immune cells and proteins in newborns show stereotypes of immune system development and its adaptation to intricate environmental exposure, among which perturbation of the gut microbiota leads to increased activated T cells in the blood. 61 Babies born by cesarean section have a relatively simple gut microbiota with fewer species than do babies born naturally. 62 In addition, the gut microbial profiles of the former group share some characteristics with their mother's skin microbial population, which is primarily composed of Staphylococcus and Corynebacterium spp., rather than the microbiota residing in the vagina, of which Lactobacillus and Prevotella spp.…”

Systems vaccinology and big data in the vaccine development chain

“…The recent progression in systems vaccinology has led to successful initiatives such as the ADITEC project 134 that provided a novel gene expression method to analyze biomarkers of tuberculosis pathogenesis 135 as well as a study where safety and immunogenicity of a novel vaccine against tuberculosis (VPM1002) were evaluated. 136 To achieve maximum vaccine efficacy and safety, future vaccine research will have to focus on target groups such as neonates 137,138 or even on the development of personalized vaccines. 139 Systems vaccinology approaches can be further applied to investigate the inter-group differences in vaccine responsiveness between healthy adults and specific target groups such as infants, and elderly or immune-deficient individuals.…”