Transcriptional changes in alveolar macrophages from adults with asthma after allergen challenge

Abstract

Under homeostatic conditions, macrophages are the most abundant immune cells in the lung. Pulmonary macrophages are a heterogeneous cell population that can be classified in at least two distinct subpopulations, that is, interstitial macrophages, located within the lung parenchyma, and alveolar macrophages (AM) which reside in the airway lumen, allowing direct contact with the environment (eg, allergens, particulate matter, and commensal bacteria). In recent years, AM have been shown to play an important role in environmental allergen-induced airway inflammation in asthma. Elimination of resident AM resulted in enhanced type 2 airway inflammation in a mouse asthma model, while depletion of blood monocytes resulted in abrogation of newly formed AM after allergen challenge and a decreased type 2 immune response. Knowledge of phenotypic alterations of AM in allergic asthma in humans is limited. In this study, we investigated the effect of house dust mite (HDM) and lipopolysaccharide (LPS) challenge on the transcriptome of AM from patients with mild asthma. We have shown previously that intrabronchial HDM/LPS challenge induces a mixed eosinophilic and neutrophil airways inflammation in asthma patients.5 Therefore, we hypothesize that exposure of AM to HDM/LPS would upregulate genes associated with eosinophil and neutrophil signalling.