Abstract
Impaired cellular innate immune defense accounts for susceptibility to sepsis and its high morbidity and mortality in preterm infants. Leukocyte recruitment is an integral part of the cellular immune response and follows a well-defined cascade of events from rolling of leukocytes along the endothelium to firm adhesion and finally transmigration which is concerted by a variety of adhesion molecules. Recent analytical advances such as fetal intravital microscopy have granted new insights into ontogenetic regulation and maturation of fetal immune cell recruitment. Understanding the fetal innate immune system is essential for targeted prevention and therapy of premature infants with severe infections or disorders of the immune system. This review gives an overview of the basic principles of leukocyte recruitment, particularly neutrophil trafficking, and its development during early life and highlights technical limitations to our current knowledge.
Highlights
Prematurity is the most prominent risk factor for neonatal diseases and death [1]
Among very immature infants, infection and sepsis are still the leading causes for mortality and morbidity [2, 5]. This may in part be explained by the immaturity of the innate immune system, which preterm infants (
Up to 60 % of extremely premature infants (
Summary
Prematurity is the most prominent risk factor for neonatal diseases and death [1]. Despite medical progress in newborn medicine, mortality remains high since the number of very low birth weight infants (≤1500 g) increases globally [2,3,4]. Intrauterine fetal immunosuppression plays a key role in preventing excessive adverse immune reactions at the feto-maternal placental border This beneficial intrauterine feature proves disadvantageous in preterm infants lacking maternal immune protection while being exposed to high levels of pathogens. After recognition of invading pathogens, leukocytes are stimulated with the primary purpose of Karenberg et al Molecular and Cellular Pediatrics (2016) 3:35 eliminating the inflammatory source This multistep process starts with the capture of circulating leukocytes from the blood stream, mostly in postcapillary venules in close proximity to inflamed tissue. The high vulnerability of preterm neonates to suffer from severe infections and sepsis can partially be attributed to impaired leukocyte recruitment early during fetal life [11]. The observation of reduced fetal leukocyte trafficking and chemotaxis is mainly explained by diminished expression of leukocyte adhesion molecules and production of cytokines at this developmental a cbdef
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