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Abstract
Understanding the ontogeny of the human immune system is a prerequisite to developing efficient and safe interventions aimed at providing long-term protection against infectious pathogens or inflammatory disorders originating early in life. The immune system of the fetus and the newborn infant had long been considered as “immature.” This insight is based on the observation that infectious diseases are often more severe or more prolonged in early life. However, studies performed in the 80s have shown that cells involved in innate immune responses develop as early as the fourth week of gestation in humans and that mature fetal T and B lymphocytes can be detected by the end of the first trimester of gestation already. More recent evidence indicates that fetal precursors are at the origin of adult tissueresident macrophages. In addition, studies of immune responses to alloantigens and pathogens in utero demonstrated that effector and regulatory responses are operational during human fetal life, further indicating that the immune system is not fundamentally immature in early life, but simply differs from immune responses observed in later life. Studies are now needed to determine the signals involved in the regulation of the functional programing of immune cells in early life and to define how these signals could be targeted to protect against infectious diseases as well as chronic inflammatory disorders. The objective of the Research Topic is to provide an overview of the current state of knowledge of the ontogeny of the immune system and of the pathogenesis of important infectious and inflammatory diseases in early life. Four themes emerged from the excellent contributions that have been assembled here.
Highlights
FETAL ORIGIN OF INNATE CELLS Recent studies indicate that a number of innate cell subsets derive from fetal progenitors and self-maintain throughout life
Myeloid cells are differently programed in early life as compared to adult life and express different levels of effector molecules involved in tissue growth and remodeling, inflammation, and induction of adaptive immune responses
KrowLucal and McCune discuss the fact that many of the functions of lymphoid and myeloid cells derived from fetal hematopoietic stem cells (HSC) are involved in barrier integrity and induction of tolerance and propose that immune maturation may proceed in a layered fashion with a fetal system predominating in utero and an adult system predominating later in life (4)
Summary
FETAL ORIGIN OF INNATE CELLS Recent studies indicate that a number of innate cell subsets derive from fetal progenitors and self-maintain throughout life. Myeloid cells are differently programed in early life as compared to adult life and express different levels of effector molecules involved in tissue growth and remodeling, inflammation, and induction of adaptive immune responses. As reviewed by Debock and Flamand, a similar development influences the functional programing of T lymphocytes, where the balance between regulatory and effector responses changes between fetal life and adult life (3).
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