Abstract
Many functions of the immune system are impaired in neonates, allowing vulnerability to serious bacterial, viral and fungal infections which would otherwise not be pathogenic to mature individuals. This vulnerability is exacerbated in compromised newborns such as premature neonates and those who have undergone surgery or who require care in an intensive care unit. Higher susceptibility of preterm neonates to infections is associated with delayed immune system maturation, with deficiencies present in both the innate and adaptive immune components. Here, we review recent insights into early life immunity, and highlight features associated with compromised newborns, given the challenges of studying neonatal immunity in compromised neonates due to the transient nature of this period of life, and logistical and ethical obstacles posed by undertaking studies newborns and infants. Finally, we highlight how the unique immunological characteristics of the premature host play key roles in the pathogenesis of diseases that are unique to this population, including necrotizing enterocolitis and the associated sequalae of lung and brain injury.
Highlights
Maturation of the immune system is a complex process that involves molecular, cellular and epigenetic programs
We have shown that TLR4 expression on the lung epithelium is required for the recruitment of proinflammatory neutrophils into the lung through the upregulation of CCL25 [50, 51], and that strategies to either inhibit TLR4 via the administration of aerosolized inhibitors, or through genetic deletion, can serve as novel lung protective strategies in the setting of necrotizing enterocolitis (NEC) [50]
Higher levels of pattern recognition receptor (PRR) expressed on epithelial cells Few Paneth cells; decreased antimicrobial peptides (AMPs) Epithelium more permeable to pathogenic bacteria Low levels High level C5a fragment Low 5% Low soluble Acute phase proteins (APPs) Comparable levels Cannot be recruited to tissue
Summary
Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Specialty section: This article was submitted to Mucosal Immunity, a section of the journal Frontiers in Immunology
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