Plasticity of the infant immune system during the perinatal period

All mammalian offspring, regardless of their developmental stage at birth, must survive the fetal-to-postnatal transition from intrauterine dependence on the mother to postnatal independence. A major challenge in this context is the allocation of limited energy resources between tissue development and growth, energy-intensive responses to infection and the establishment of host-microbial homeostasis. For a long time, it was thought that early-life immunity was immature and dysfunctional. It is only recently that we have begun to understand, at a mechanistic level, how perinatal immunity is tailored to mediate the transition to postnatal life. This adaptation requires a high degree of temporal plasticity, which integrates the developmental trajectories of immune cells, changes in barrier permeability, effects of the microbiota, the waning contribution of maternal immunity and effects of early-life antigen exposure. This Review analyses the existing evidence for perinatal immune plasticity and its underlying mechanisms and consequences, with a particular focus on myeloid cells and barrier immunity. It synthesizes models as to how this immune plasticity may be induced, maintained and therapeutically modulated, even beyond infancy, while highlighting interspecies differences and commonalities, as well as current research needs.