Neutrophil polarization in the airways of infants with bronchiolitis

Abstract

Abstract Pulmonary neutrophilia is observed in pediatric patients with viral-induced bronchiolitis. Despite an alleviation in clinical symptoms, our findings suggest that airway neutrophil infiltration and activation does not appear to resolve by discharge in hospitalized infants. The recent identification of neutrophil plasticity and polarization into distinct phenotypic pro-inflammatory (N1) and immunosuppressive (N2) subsets provides an unexplored avenue for regulation of the neutrophilic inflammatory response in bronchiolitis. Admission nasopharyngeal aspirate (NPA) samples were assessed from twelve bronchiolitic infants presenting to Flinders Medical Centre, Adelaide, Australia in 2013. An overall strong positive correlation between N2 soluble mediator TGF-β1 and the percentage of neutrophils stained for N2 marker MMP-9 was observed; with no correlation observed between TGF-β1 and neutrophils positive for N1 marker ICAM-1. In 2015 and 2016, eleven bronchiolitic infants provided consecutive NPAs across hospitalization. In both cohorts, concentrations of active TGF-β1 detected were comparable to levels previously identified to significantly suppress neutrophil activity in vitro (>1 pg/mL). Temporal assessment of neutrophil polarization is underway. The detection of pre-established neutrophil polarizing mediators, and the correlation of these mediators with different neutrophilic subsets within NPAs indicates a potential N1/N2 paradigm occurring within the airways of bronchiolitic infants. Further investigation is merited, with analyses over disease trajectory and by disease severity required to assess biological significance.