Early Microbial–Immune Interactions and Innate Immune Training of the Respiratory System during Health and Disease

Over the past two decades, several studies have positioned early-life microbial exposure as a key factor for protection or susceptibility to respiratory diseases. Birth cohorts have identified a strong link between neonatal bacterial colonization of the nasal airway and gut with the risk for respiratory infections and childhood asthma. Translational studies have provided companion mechanistic insights on how viral and bacterial exposures in early life affect immune development at the respiratory mucosal barrier. In this review, we summarize and discuss our current understanding of how early microbial–immune interactions occur during infancy, with a particular focus on the emergent paradigm of “innate immune training”. Future human-based studies including newborns and infants are needed to inform the timing and key pathways implicated in the development, maturation, and innate training of the airway immune response, and how early microbiota and virus exposures modulate these processes in the respiratory system during health and disease.