TLR5 Activation Exacerbates Airway Inflammation in Asthma.
Lung
; 198(2): 289-298, 2020 04.
Article
in En
| MEDLINE
| ID: mdl-32060608
ABSTRACT
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.CONCLUSION:
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).Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asthma
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Bronchoconstriction
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Bronchial Hyperreactivity
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Toll-Like Receptor 5
/
Lung
Type of study:
Observational_studies
/
Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Lung
Year:
2020
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA