TLR5 Activation Exacerbates Airway Inflammation in Asthma
| Autor: | Gregory S. Whitehead, Donald N. Cook, R Fannin, Cynthia L. Innes, Stavros Garantziotis, Carol S. Trempus, Salik Hussain, Shepherd H. Schurman |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Lipopolysaccharide Ovalbumin Bronchoconstriction Polymorphism Single Nucleotide Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine immune system diseases Polymorphism (computer science) Animals Humans Medicine 030212 general & internal medicine Receptor Lung Asthma Innate immune system biology business.industry Middle Aged Th1 Cells medicine.disease respiratory tract diseases Mice Inbred C57BL Disease Models Animal Toll-Like Receptor 5 Cross-Sectional Studies HEK293 Cells 030228 respiratory system chemistry TLR5 Case-Control Studies Immunology biology.protein Cytokines Female Bronchial Hyperreactivity business Flagellin Signal Transduction |
| Zdroj: | Lung |
| ISSN: | 1432-1750 0341-2040 |
| DOI: | 10.1007/s00408-020-00337-2 |
| Popis: | INTRODUCTION: Innate immune activation through exposure to indoor and outdoor pollutants is emerging as an important determinant of asthma severity. For example, household levels of the bacterial product lipopolysaccharide (LPS) are associated with increased asthma severity. We hypothesized that activation of the innate immune receptor TLR5 by its bacterial ligand flagellin will exacerbate airway inflammation and asthma symptoms. METHODS: We determined the effect of flagellin co-exposure with ovalbumin in a murine model of allergic asthma. We evaluated the presence of flagellin activity in house dust of asthma patients. Finally, we analyzed the association of a dominant-negative polymorphism in TLR5 (rs5744168) with asthma symptoms in patients with asthma. RESULTS: We showed that bacterial flagellin can be found in the house dust of patients with asthma and that this bacterial product exacerbates allergic airway inflammation in an allergen-specific mouse model of asthma. Furthermore, a dominant-negative genetic polymorphism in TLR5, the receptor for flagellin, is associated with decreased symptoms in patients with asthma. CONCLUSIONS: Together, our results reveal a novel genetic protective factor (TLR5 deficiency) and a novel environmental pollutant (microbial flagellin) that influence asthma severity. (Clinical trials NCT01688986 and NCT01087307). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink