Immune sensing of aeroallergen-associated double-stranded RNA triggers an IFN response and modulates type 2 lung inflammation

Li She, Hamad H. Alanazi, Liping Yan, Yi Zou, Yilun Sun, Peter H. Dube, Edward G. Brooks, Gema D. Barrera, Zhao Lai, Yidong Chen, Yong Liu, Xin Zhang, Xiao Dong Li

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The innate immune sensing of allergens or allergen-associated components regulate the development of type 2 inflammatory responses. However, the underlying molecular basis by which allergens or allergen-associated components are detected by innate immune receptors remains elusive. In this study, we report that the most common aeroallergen, house dust mite (HDM), harbors a dsRNA species (HDM-dsRNA) that can activate TLR3-mediated IFN responses and counteract the development of an uncontrolled type 2 immune response. We demonstrate that the mouse strains defective in the dsRNA-sensing pathways show aggravated type 2 inflammation defined by severe eosinophilia, elevated level of type 2 cytokines, and mucus overproduction in a model of allergic lung inflammation. The inability to sense HDM-dsRNA resulted in significant increases in airway hyperreactivity. We further show that the administration of the purified HDM-dsRNA at a low dose is sufficient to induce an immune response to prevent the onset of a severe type 2 lung inflammation. Collectively, these results unveil a new role for the HDM-dsRNA/TLR3-signaling axis in the modulation of a type 2 lung inflammation in mice.

Original languageEnglish (US)
Pages (from-to)2520-2531
Number of pages12
JournalJournal of Immunology
Volume203
Issue number9
DOIs
StatePublished - Nov 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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