House Dust Mite Allergen Induces Asthma Via Toll-like Receptor 4 Triggering of Airway Structural Cells

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2009 Mar 31

PMID 19330007

Citations 538

Authors

Hamida Hammad

Marcello Chieppa

Frederic Perros

Monique A Willart

Ronald N Germain

Bart N Lambrecht

Affiliations

Soon will be listed here.

Abstract

Barrier epithelial cells and airway dendritic cells (DCs) make up the first line of defense against inhaled substances such as house dust mite (HDM) allergen and endotoxin (lipopolysaccharide, LPS). We hypothesized that these cells need to communicate with each other to cause allergic disease. We show in irradiated chimeric mice that Toll-like receptor 4 (TLR4) expression on radioresistant lung structural cells, but not on DCs, is necessary and sufficient for DC activation in the lung and for priming of effector T helper responses to HDM. TLR4 triggering on structural cells caused production of the innate proallergic cytokines thymic stromal lymphopoietin, granulocyte-macrophage colony-stimulating factor, interleukin-25 and interleukin-33. The absence of TLR4 on structural cells, but not on hematopoietic cells, abolished HDM-driven allergic airway inflammation. Finally, inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma, including bronchial hyperreactivity. Our data identify an innate immune function of airway epithelial cells that drives allergic inflammation via activation of mucosal DCs.

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