The early life education of the immune system: Moms, microbes and (missed) opportunities

The early life immune system is characterized by unique developmental milestones. Functionally diverse immune cells arise from distinct waves of hematopoietic stem cells, a phenomenon referred to as ‘layered’ immunity. This stratified development of immune cells extends to lineages of both innate and adaptive cells. The defined time window for the development of these immune cells lends itself to the influence of specific exposures typical of the early life period. The perinatal immune system develops in a relatively sterile fetal environment but emerges into one filled with a multitude of antigenic encounters. A major burden of this comes in the form of the microbiota that is being newly established at mucosal surfaces of the newborn. Accumulating evidence suggests that early life microbial exposures, including those arising in utero, can imprint long-lasting changes in the offspring’s immune system and determine disease risk throughout life. In this review, I highlight unique features of early life immunity and explore the role of intestinal bacteria in educating the developing immune system.