Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease
Lynne R Prince1, Nicola C Maxwell2, Sharonjit K Gill1
1Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom.
Insights
Preterm infants show altered airway immune cell phenotypes, with immature macrophages potentially linked to chronic lung disease progression. Phenotyping these cells may predict disease outcomes in premature infants.
Area of Science:
- Neonatal immunology
- Pulmonology
- Innate immunity
Background:
- The causes of persistent lung inflammation in premature infants with chronic lung disease of prematurity (CLD) are not well understood, hindering prognosis and treatment stratification.
- Airway macrophages are key innate immune cells involved in initiating and resolving inflammation.
Purpose of the Study:
- To investigate the phenotypes of airway innate immune cells in preterm infants diagnosed with respiratory distress syndrome (RDS) or CLD.
- To explore the relationship between gestational maturity and macrophage polarization in the airways of infants.
Main Methods:
- Bronchoalveolar lavage (BAL) fluid was collected from both term and preterm infants requiring mechanical ventilation.
- Flow cytometry was employed to phenotype the collected BAL cells, focusing on monocyte and macrophage populations.
Main Results:
- Preterm infants had a higher proportion of non-classical CD14(+)/CD16(+) monocytes at birth compared to term infants (58.9% vs 33.0%).
- Infants with RDS exhibited more CD36(+) macrophages than those with CLD (70.3% vs 37.6%).
- By day 3, lower gestational age infants had more CD14(+) mononuclear phagocytes but reduced functional polarization (HLA-DR, CD36), suggesting impaired maturation or increased recruitment.
Conclusions:
- Macrophage polarization in the airways appears influenced by gestational maturity.
- Immature macrophage phenotypes may correlate with the progression from RDS to CLD.
- Phenotyping airway mononuclear cells via BAL could serve as a predictive tool for disease outcomes in preterm infants.
Background:
The 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.
Objectives:
To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.
Methods:
Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.
Results:
Preterm 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.
Conclusions:
These 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.
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