Format

Send to

Choose Destination
Lung. 2020 Apr;198(2):289-298. doi: 10.1007/s00408-020-00337-2. Epub 2020 Feb 14.

TLR5 Activation Exacerbates Airway Inflammation in Asthma.

Author information

1
Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
2
Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, 26506, USA.
3
Molecular Genomics Core Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
4
Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
5
Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA. garantziotis@niehs.nih.gov.
6
Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA. garantziotis@niehs.nih.gov.

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).

KEYWORDS:

Airway inflammation; Asthma; Flagellin; TLR5

PMID:
32060608
DOI:
10.1007/s00408-020-00337-2

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center