Ontogeny, dynamics, and characteristics of neutrophils during the perinatal period.

Abstract

This review examines the dynamic development and unique characteristics of neutrophils during the perinatal period, a critical window when the immune system undergoes rapid reprogramming, based on the mouse studies. In the mouse fetal liver-the primary hematopoietic niche before birth-hematopoietic stem cells and progenitor cells expand in parallel, with granulocyte-monocyte progenitors preferentially differentiating into neutrophils during late gestation. This process, partly driven by granulocyte colony-stimulating factor (G-CSF), substantially increases the number of neutrophils, preparing the neonates for microbial challenges after birth. After birth, there is a surge in circulating neutrophils, likely due to the mobilization of neutrophils from the liver, followed by a microbiota-dependent activation of granulopoiesis in the bone marrow. In addition to their antimicrobial functions, neonatal neutrophils exhibit immunomodulatory characteristics, such as reduced pro-inflammatory signaling and diminished neutrophil extracellular trap formation. These traits may contribute to tolerance to the microbes and help mitigate excessive inflammation. Finally, unresolved issues related to the phenotypic diversity and precise physiological roles of neutrophils during the perinatal period are addressed, highlighting the need for further research. Teaser abstract This review examines the dynamic development of neutrophils during the perinatal period, mainly based on the mouse studies. In the mouse fetal liver, hematopoietic stem and progenitor cells expand in parallel, and neutrophils massively accumulate, preparing neonates for postnatal microbial challenges. After birth, neutrophil numbers surge due to liver mobilization and subsequent microbiota-driven bone marrow granulopoiesis. In addition to their antimicrobial role, neonatal neutrophils display immunomodulatory features that may help control excessive inflammation. Unresolved issues regarding their diversity and functions are addressed.