Age-Appropriate Functions and Dysfunctions of the Neonatal Neutrophil

Abstract

Neonatal and adult neutrophils are distinctly different from one another due to well-defined and documented deficiencies in neonatal cells, including impaired functions, reduced concentrations of microbicidal proteins and enzymes necessary for pathogen destruction, and variances in cell surface receptors. Neutrophil maturation is clearly demonstrated throughout pregnancy from the earliest hematopoietic precursors in the yolk sac to the well-developed myeloid progenitor cells in the bone marrow around the seventh month of gestation. Notable deficiencies of neonatal neutrophils are generally correlated with gestational age and clinical condition, so that the least functional neutrophils are found in the youngest, sickest neonates. Interruption of normal gestation secondary to preterm birth exposes these shortcomings and places the neonate at an exceptionally high rate of infection and sepsis-related mortality. Because the fetus develops in a sterile environment, neonatal adaptive immune responses are deficient from lack of antigen exposure in utero. Newborns must therefore rely on innate immunity to protect against early infection. Neutrophils are a vital component of innate immunity since they are the first cells to respond to and defend against bacterial, viral, and fungal infections. However, notable phenotypic and functional disparities exist between neonatal and adult cells. Below is review of neutrophil ontogeny, as well as a discussion regarding known differences between preterm and term neonatal and adult neutrophils with respect to cell membrane receptors and functions. Our analysis will also explain how these variations decrease with postnatal age.

Neutrophil chemotaxis and transcriptomics in term and preterm neonates

“…Prior studies have suggested microbial exposure and labor may have influential roles in neutrophil function. Specifically, some investigators believe that neonatal neutrophils reside in a “pre-primed” state and become reactive following labor [33]. Despite preterm neonates being exposed to these potentially activating factors, preterm neutrophils still demonstrated deficiencies in chemotaxis and transcriptomics.…”

Strong Positive Correlation between Neutrophil-to-lymphocyte Ratio and C-reactive Protein in Early Onset Sepsis

“…Physiologically, these facts correlate with gestational age, leading to a high rate of infection during neonatal period. 4 With these conditions, lower NLR value was observed in the EOS group when compared to the non-EOS group. The CRP level showed the same pattern as NLR, and demonstrated a strong positive correlation with NLR in premature infants with EOS.…”

“…1 This weak neonatal neutrophil responses are associated with gestational age and neonatal clinical conditions with youngest and sickest neonates show the lack of neutrophil functions. 4 On the other hand, there is a low absolute number of circulating lymphocytes in premature infants that leads to clonal expansion with most are naïve T cells. 6 Immunosuppresion of anti-inflammatories that relates to this condition is also seen while while many lymphocytes undergo apoptosis.…”

“…Neutrophils also discharge cytokine and activate T-cell. 4 Along with the phenomenon, a rise in anti-inflammatory cytokines will lead to immunosuppression, and induce apoptosis of a certain number of lymphocytes. Thus, lymphopenia state is an indicator of immunosuppression that may lead to sepsis.…”

Immunometabolism and innate immunity in the context of immunological maturation and respiratory pathogens in young children

“…Furthermore, there are other limitations such as diminished respiratory bursts, chemotaxis, and responses to stress in neonates/infants that do not occur in adults . Moreover, there is also lower neonatal and infant neutrophil release of many bactericidal proteins despite having similar concentrations of defensins and myeloperoxidase . Whether these responses are outgrown in the toddler and any mechanisms is not well known, but it could be assumed that the neutrophils will have some gain in function but will, likely, remain lower than adults.…”