Programmed and environmental determinants driving neonatal mucosal immune development

The mucosal immune system of neonates goes through successive, non-redundant phases that support the developmental needs of the infant and ultimately establish immune homeostasis. These phases are informed by environmental cues, including dietary and microbial stimuli, but also evolutionary developmental programming that functions independently of external stimuli. The immune response to exogenous stimuli is tightly regulated during early life; thresholds are set within this neonatal “window of opportunity” that govern how the immune system will respond to diet, the microbiota, and pathogenic microorganisms in the future. Thus, changes in early-life exposure, such as breastfeeding or environmental and microbial stimuli, influence immunological and metabolic homeostasis and the risk of developing diseases such as asthma/allergy and obesity. Neonatal development of mucosal immunity is a carefully regulated process that both influences and responds to progressive microbial exposure in the infant intestines. Hand, Hornef and colleagues review how the phases of mucosal development provide important and non-redundant functions toward establishing immediate and long-term immune homeostasis.