Dysfunction of innate immunity and associated pathology in neonates

Abstract

The neutrophils and complement system are the critical elements of innate immunity mainly due to participation in the first line of defense against microorganisms by means of phagocytosis, lysis of bacteria and activation of naive B-lymphocytes. In this report we provide an overview of the up to date information regarding the neutrophil and complement system's functional ability in newborn infants in association with the maternal conditions that exist during the intrauterine stage, gestational age and post-neonatal pathology. The neonates' capacity to control the neutrophil and complement protein activation process has also been discussed because of the evidence that uncontrolled activation of these immune elements provides a significant contribution to the tissue damage and subsequent pathology. The authors are confident that despite the many unanswered questions this review updates their knowledge and points the need for further research to clarify the role of the age-associated dysfunction of neutrophils and complement system in the infection and inflammation related pathology of newborn infants.

The changing spectrum of neonatal infectious disease

“…Dysfunction in the naïve neutrophil has also been implicated in contributing to the pathology and severity of neonatal sepsis. [25][26][27][28] Although term infants can mount adult-like immune responses, [29][30][31][32] these occur under specific sets of circumstances and cannot be relied upon to be protective. Adding to the risk of infection in the preterm infant is the fact that they have failed to acquire protective maternal antibodies that would have been transferred during the late third trimester of pregnancy.…”

Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates

“…10,11 Neonatal PMN dysfunction is multifactorial, in part depending on the degree of prematurity, and is only partially characterized. 10,11,18 There is no established surrogate model of neonatal neutrophil dysfunction, although altered PMN responses to noninfectious stimuli have been reported in neonatal mice. 19 PMNs isolated from premature human neonates have impaired phagocytosis, decreased capacity to generate oxygen radicals, and deficient intracellular bacterial killing compared with neutrophils from healthy adults when studied in the apparent absence of physiologic stress or infectious challenge to the infant.…”

“…As an example, neonatal PMN dysfunction is thought to be a pivotal feature of sepsis in the newborn. [9][10][11] The incidence of neonatal sepsis is estimated to be 1 to 5 cases per 1000 live births in the United States and to be even higher after very low birth weight premature deliveries (15-19/1000); in contrast, the incidence of sepsis is much lower in children older than 1 year of age and in young adults. [12][13][14][15] Furthermore, the incidence of neonatal sepsis is as high as 25% in some areas of the developing world.…”

“…16,17 Thus, neonatal PMN dysfunction is a contributor to a public health problem of significant proportions, and also may precipitate other severe infectious syndromes. 10,11 Neonatal PMN dysfunction is multifactorial, in part depending on the degree of prematurity, and is only partially characterized. 10,11,18 There is no established surrogate model of neonatal neutrophil dysfunction, although altered PMN responses to noninfectious stimuli have been reported in neonatal mice.…”

“…19 PMNs isolated from premature human neonates have impaired phagocytosis, decreased capacity to generate oxygen radicals, and deficient intracellular bacterial killing compared with neutrophils from healthy adults when studied in the apparent absence of physiologic stress or infectious challenge to the infant. 11,18,20 Whereas neutrophils from full-term infants have normal phagocytosis, oxidant generation, and intracellular bacterial killing when examined under basal conditions, antibacterial functions are dramatically impaired when PMNs isolated from babies with suspected sepsis or respiratory distress are studied. 21 Thus, defects in antimicrobial capacity are basally present in neutrophils from premature neonates and are detected in PMNs from term neonates when the infants are infected or subjected to physiologic stress or inflammatory challenge.…”