Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny

Abstract

Infections in the first year of life are common and often severe. The newborn host demonstrates both quantitative and qualitative differences to the adult in nearly all aspects of immunity, which at least partially explain the increased susceptibility to infection. Here we discuss how differences in susceptibility to infection result not out of a state of immaturity, but rather reflect adaptation to the particular demands placed on the immune system in early life. We review the mechanisms underlying host defense in the very young, and discuss how specific developmental demands increase the risk of particular infectious diseases. In this context, we discuss how this plasticity, i.e. the capacity to adapt to demands encountered in early life, also provides the potential to leverage protection of the young against infection and disease through a number of interventions.

Regulation of inflammation by microbiota interactions with the host

“…In humans, early TLR5 expression directly correlates with the magnitude of the antibody response to the trivalent inactivated influenza vaccine 122 . Numerous vaccines and boosters are administered to children within the first 15 months of life, when the microbiota is highly sensitive to environmental factors such as hygiene, breast milk versus formula diet, and vaginal versus Caesarean-section delivery 123,124 . Emerging considerations in determining vaccination efficacy are the microbiota composition and diversity, as well as the therapeutic potential of the critical perinatal period to imprint protective host defenses in adult life.…”

Impact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming

“…The profile of the immune system and the magnitude of its responses vary significantly with gestational and post birth age. Greater details about the cellular ontogeny and developmental timing of immune cells in utero can be obtained from these reviews . Fetal hematopoiesis occurs in distinct spatial and temporal sites: the extraembryonic yolk sac, the fetal liver, and the bone marrow (Fig.…”

Immunometabolism and innate immunity in the context of immunological maturation and respiratory pathogens in young children

“…Although neonatal neutrophils exhibit strong phagocytic activity against gram‐positive bacteria, their ability to do so against gram‐negative bacteria appears impaired as compared with adults . Furthermore, there are other limitations such as diminished respiratory bursts, chemotaxis, and responses to stress in neonates/infants that do not occur in adults . Moreover, there is also lower neonatal and infant neutrophil release of many bactericidal proteins despite having similar concentrations of defensins and myeloperoxidase .…”