House dust mite allergen induces asthma via TLR4 triggering of airway structural cells

By H. Hammad, M. Chieppa, F. Perros, M. Willart, Ronald N. Germain, B. Lambrecht. Nature Medicine, 2009

1,123 citations recorded by the source corpus.

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.

Subfields: Immunology, Immunology and Allergy, Physiology

View Paper: https://www.semanticscholar.org/paper/d2e9a720cd630599fda9c33150525dfe46bd35bd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. H. Hammad
2. B. Lambrecht
3. Jinfang Zhu
4. W. E. Paul
5. M. Willart
6. Shane Crotty

In Physiology

1. H. Hammad
2. B. Lambrecht

Citations in the corpus

• DAMPening Inflammation by Modulating TLR Signalling (2010, background): “Interestingly, in the absence of MD-2, the LPS-dependent TLR4 signalling can be reconstituted by the mite dust allergen Der p 2, which has structural and functional homology with MD-2 and mimics the activity of MD-2 by presenting LPS to TLR4 [58, 59].”
• Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen (2010, background): “We favor a model in which basophils amplify Th2 immunity to HDM, initiated by DCs and instructed by innate signaling through TLR4 and Myd88 signaling and C-type lectin signaling on epithelial cells and dendritic cells (Hammad et al., 2009; Nathan et al., 2009; Trompette et al., 2009).”
• How are TH2-type immune responses initiated and amplified? (2010, background): “Recently, it has been reported that Toll-like receptor 4 (TLR4) expression by lung cells (probably lung epithelial cells), but not DCs, is necessary and sufficient for HDM allergen-mediated DC activation and T H 2 cell differentiatio”