House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells

Hamida Hammad, Marcello Chieppa, Frederic Perros, Monique A. Willart, Ronald N. Germain, Bart N. Lambrecht

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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.

Original languageEnglish
Pages (from-to)410-416
Number of pages7
JournalNature Medicine
Volume15
Issue number4
DOIs
Publication statusPublished - Apr 2009

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Dermatophagoides Antigens
Toll-Like Receptor 4
Asthma
Dendritic Cells
Pyroglyphidae
Epithelial Cells
Dust
Chemical activation
Interleukin-17
Inflammation
Bronchial Hyperreactivity
Granulocyte-Macrophage Colony-Stimulating Factor
Lung
Endotoxins
Lipopolysaccharides
Inhalation
Cytokines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hammad, H., Chieppa, M., Perros, F., Willart, M. A., Germain, R. N., & Lambrecht, B. N. (2009). House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nature Medicine, 15(4), 410-416. https://doi.org/10.1038/nm.1946

House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. / Hammad, Hamida; Chieppa, Marcello; Perros, Frederic; Willart, Monique A.; Germain, Ronald N.; Lambrecht, Bart N.

In: Nature Medicine, Vol. 15, No. 4, 04.2009, p. 410-416.

Research output: Contribution to journalArticle

Hammad, H, Chieppa, M, Perros, F, Willart, MA, Germain, RN & Lambrecht, BN 2009, 'House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells', Nature Medicine, vol. 15, no. 4, pp. 410-416. https://doi.org/10.1038/nm.1946
Hammad, Hamida ; Chieppa, Marcello ; Perros, Frederic ; Willart, Monique A. ; Germain, Ronald N. ; Lambrecht, Bart N. / House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. In: Nature Medicine. 2009 ; Vol. 15, No. 4. pp. 410-416.
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