Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment

Abstract

Although classically characterized by chronic airway inflammation with eosinophil infiltration, asthma is a complex and multifactorial condition with numerous clinical phenotypes. Epidemiological studies strongly support the link between obesity and asthma and suggest that obesity precedes and promotes asthma development, increases asthma severity, and reduces steroid responsivity. Using a house dust mite (HDM) model of airway hyperresponsiveness in C57BL/6 mice, we examined the effects of diet-induced obesity on allergic airway inflammation and its treatment with dexamethasone. When compared to lean mice treated with HDM, obese-HDM mice had reduced plasma adiponectin, an anti-inflammatory adipokine, lower eosinophil and higher macrophage infiltration into the lungs and bronchoalveolar lavage (BAL) fluid, increased expression of total, M1, and M2 macrophage markers in the lungs, and enhanced Th2 and non-Th2 cytokine expression in the lungs. While Th2-associated responses in obese-HDM mice were suppressed by systemic dexamethasone, several Th2-independent responses, including total and M1 macrophage markers in the lungs, and lung CXC-motif ligand 1 (CXCL1) levels, were not improved following dexamethasone treatment. Thus, HDM combined with obesity promotes mixed localized inflammatory responses (e.g., M1, M2, Th1, and Th2) and shifts the cellular infiltration from eosinophils to macrophages, which are less sensitive to dexamethasone regulation. Because obese asthmatics exhibit more severe symptoms, lack a predominance of Th2 biomarkers, and are predicted to experience more steroid resistance when compared to lean asthmatics, this model could be used to study blunted steroid responses in obese-HDM mice and to define the macrophages found in the lungs.

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Abbreviations

ANOVA:

Analysis of variance

BAL:

Bronchoalveolar lavage

CXCL1:

CXC-motif ligand 1

Dex:

Dexamethasone

GRα:

Glucocorticoid receptor alpha

GRβ:

Glucocorticoid receptor beta

HDM:

House dust mite

H&E:

Hematoxylin and eosin

HFD:

High-fat diet

qPCR:

Quantitative polymerase chain reaction

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Acknowledgments

JD and LH were Fellows supported by a T32 training grant (AI083223-06, V Bonagura PI), the Feinstein Institute for Medical Research, and Hofstra North Shore-LIJ School of Medicine (LW).

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Correspondence to C. N. Metz.

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Diaz, J., Warren, L., Helfner, L. et al. Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment. Immunol Res 63, 197–208 (2015). https://doi.org/10.1007/s12026-015-8717-2

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Keywords

  • Asthma
  • Steroid resistance
  • Airway inflammation
  • Diet-induced obesity