Comprehensive analysis of lung macrophages and dendritic cells in two murine models of allergic airway inflammation reveals model- and subset-specific accumulation and phenotypic alterations.

ABSTRACT

Introduction: Allergic asthma has been mainly attributed to T helper type 2 (Th2) and proinflammatory responses but many cellular processes remain elusive. There is increasing evidence for distinct roles for macrophage and dendritic cell (DC) subsets in allergic airway inflammation (AAI). At the same time, there are various mouse models for allergic asthma that have been of utmost importance in identifying key inflammatory pathways in AAI but that differ in the allergen and/or route of sensitization. It is unclear whether and how the accumulation and activation of specialized macrophage and DC subsets depend on the experimental model chosen for analyses. Methods: In our study, we employed high-parameter spectral flow cytometry to comprehensively assess the accumulation and phenotypic alterations of different macrophage- and DC-subsets in the lung in an OVA- and an HDM-mediated mouse model of AAI. Results: We observed subset-specific as well as model-specific characteristics with respect to cell numbers and functional marker expression. Generally, alveolar as opposed to interstitial macrophages showed increased MHCII surface expression in AAI. Between the models, we observed significantly increased numbers of alveolar macrophages, CD103+ DC and CD11b+ DC in HDM-mediated AAI, concurrent with significantly increased airway interleukin-4 but decreased total serum IgE levels. Further, increased expression of CD80 and CD86 on DC was exclusively detected in HDM-mediated AAI. Discussion: Our study demonstrates a model-specific involvement of macrophage and DC subsets in AAI. It further highlights spectral flow cytometry as a valuable tool for their comprehensive analysis under inflammatory conditions in the lung.