Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models.

Müge Özkan,Gerhard Wingender,Yusuf Cem Eskiocak

doi:10.1371/journal.pone.0250533

Abstract

Asthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7+ activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.

Highlights

Asthma is a chronic airway inflammation with often debilitating impacts on the health of patients
For serum IgE, higher levels were reported in eosinophilic asthma patients than in neutrophilic asthma patients [29, 30], and αIgE therapy was effective for eosinophilic asthma [29, 31]
A better understanding of the immunological features and underlying immunopathology of the different asthma endotypes is expected to lead the way to improved therapies

Summary

Introduction

Asthma is a chronic airway inflammation with often debilitating impacts on the health of patients. Type 2-high or eosinophilic asthma is the best-understood endotype and is often triggered by inhaled antigens, like house dust mites (HDM), ragweed pollen, mold, or cockroach proteins [1, 4]. This eosinophilic asthma is characterized by (i) elevated levels of eosinophils (eosinophilia) and mast cells in the bronchia, by (ii) a type 2-polarized immune response, with the production of Th2 cytokines, like IL-4, IL-5, and IL13, and by (iii) an augmented production of antigen-specific IgE antibodies [1, 5, 6].

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Conclusion