Macrophage Phenotype Is Associated with Disease Severity in Preterm Infants with Chronic Lung Disease

Abstract

BackgroundThe etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.ObjectivesTo investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.MethodsBronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.ResultsPreterm birth was associated with an increase in the proportion of non-classical CD14+/CD16+ monocytes on the day of delivery (58.9±5.8% of total mononuclear cells in preterm vs 33.0±6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36+ macrophages compared with the CLD group (70.3±5.3% in RDS vs 37.6±8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14+ mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung.ConclusionsThese findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.

Resident alveolar macrophages are master regulators of arrested alveolarization in experimental bronchopulmonary dysplasia

“…It is therefore proposed here that after hyperoxia exposure, rAMs transdifferentiate into the cells of Pop3, and these activated ‘rAMs’ may causally contribute to arrested alveolarization. This idea is supported by the observations that macrophages from lavage fluids from neonates with BPD exhibit phenotypic plasticity , and that increased expression of MHCII on pulmonary macrophages was noted in lungs from preterm infants who died with BPD . In sum, this is the first report that macrophages are causal contributors to pathological lung development.…”

Infant Alveolar Macrophages Are Unable to Effectively Contain Mycobacterium tuberculosis

“…AMφs are known to express a unique combination of phenotypic markers due to the influence of the airway microenvironment (2), but few reports have described the immunophenotype of human infant AMφs (23). We measured surface marker expression of AMφs from seven infants and seven adults (Figure 1).…”

Development of allergic immunity in early life

“…Preterm infants had increased proportions of non-classical CD14 + CD16 + monocytes at birth, and immature macrophage phenotypes were associated with progression from respiratory distress syndrome to chronic lung disease of prematurity. 75 Preterm infants with resolving lung injury had greater proportions of mature macrophages, than those with progressive lung disease. Since these types of studies rely on lavage of ventilated, intubated babies, there is no information regarding the phenotype of macrophages during normal human perinatal development or on the impact of phenotype on development of asthma in subsequent childhood.…”

“…Some studies have used bronchial lavage samples from babies requiring mechanical ventilation during chronic infections, and suggested that phenotypic maturation of monocyte populations was associated with gestational age. Preterm infants had increased proportions of non‐classical CD14 + CD16 + monocytes at birth, and immature macrophage phenotypes were associated with progression from respiratory distress syndrome to chronic lung disease of prematurity . Preterm infants with resolving lung injury had greater proportions of mature macrophages, than those with progressive lung disease.…”