Immune-microbe interactions early in life: A determinant of health and disease long term

Research on newborn immunity has revealed the importance of cell ontogeny, feto-maternal tolerance, and the transfer of maternal antibodies. Less is known about postnatal adaptation to environmental exposures. The microbiome and its importance for health have been extensively studied, but it remains unclear how mutually beneficial relationships between commensal microbes and human cells first arise and are maintained throughout life. Such immune-microbe mutualism, and perturbations thereof, is most likely a root cause of increasing incidences of immune-mediated disorders such as allergies and autoimmunity across many industrialized nations during the past century. In this Review, I discuss our current understanding of immune development and propose that mismatches among ancestral, early-life, and adult environments can explain perturbations to immune-microbe interactions, immune dysregulation, and increased risks of immune-mediated diseases.