Peripheral blood mononuclear cell (PBMC) gene expression in human infants shifts from innate to adaptive immunity in the first six months of life (247.5)

The newborn immune system is developmentally naïve, but undergoes rapid maturation upon exposure to environmental antigens. As part of a clinical trial in infants aimed at assessing how diet impacts PBMC transcriptome, genes that were developmentally regulated independent of diet‐ were discovered. Blood samples were obtained from breast‐fed (n=60) and three sets of formula‐fed (n=186 total) infants at 1, 4 and 6 mos of age. PBMC were isolated, RNA extracted and gene expression assessed using the Affymetrix HuGene 2.0ST gene chip. To evaluate patterns of gene expression, Weighted Gene Correlation Network Analysis (WGCNA) was performed on 6,441 probe sets with an overall 4x3 ANOVA FDR p‐value<0.3. Three gene clusters with similar patterns of expression in each diet (1 vs. 4 & 6 mos) encompassing 1085 genes were identified. Functional analysis was performed with MetaCore. Pathways with higher expression at 1‐mo reflected cellular proliferation, innate defense processes (defensins, hydrogen peroxide‐induced killing) and Th17‐derived cytokines. By 4‐ to 6‐mos of age, genes associated with humoral immunoglobulin‐mediated immunity and interferon and IL‐4 signaling predominated. These data illustrate for the first time the developmental ontogeny of gene expression in circulating immune cells of human infants. Grant Funding Source : Arla Foods and Biostime