The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens

Rhonda H. Wilson, Shuichiro Maruoka, Gregory S. Whitehead, Julie F. Foley, Gordon P. Flake, Michelle L. Sever, Darryl C. Zeldin, Monica Kraft, Stavros Garantziotis, Hideki Nakano, Donald N. Cook

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction. Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria. The ability of bacterial products to act as adjuvants suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen-presenting dendritic cells (DCs) in vitro and promote allergic sensitization to inhaled innocuous proteins in vivo. It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen for adjuvant activity of microbial products revealed that the bacterial protein flagellin (FLA) stimulated strong allergic airway responses to an innocuous inhaled protein, ovalbumin (OVA). Moreover, Toll-like receptor 5 (TLR5), the mammalian receptor for FLA, was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, individuals with asthma have higher serum levels of FLA-specific antibodies as compared to nonasthmatic individuals. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens.

Original languageEnglish (US)
Pages (from-to)1705-1710
Number of pages6
JournalNature Medicine
Volume18
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

Fingerprint

Toll-Like Receptor 5
Flagellin
Allergens
Asthma
Ligands
Dust
Bacterial Proteins
Ovalbumin
Aptitude
Antigen-Presenting Cells
Airway Obstruction
Mucus
Bacteria
Proteins
Gram-Negative Bacteria
Dendritic Cells
Pneumonia
Antigens
Antibodies
Serum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wilson, R. H., Maruoka, S., Whitehead, G. S., Foley, J. F., Flake, G. P., Sever, M. L., ... Cook, D. N. (2012). The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens. Nature Medicine, 18(11), 1705-1710. https://doi.org/10.1038/nm.2920

The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens. / Wilson, Rhonda H.; Maruoka, Shuichiro; Whitehead, Gregory S.; Foley, Julie F.; Flake, Gordon P.; Sever, Michelle L.; Zeldin, Darryl C.; Kraft, Monica; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N.

In: Nature Medicine, Vol. 18, No. 11, 01.11.2012, p. 1705-1710.

Research output: Contribution to journalArticle

Wilson, RH, Maruoka, S, Whitehead, GS, Foley, JF, Flake, GP, Sever, ML, Zeldin, DC, Kraft, M, Garantziotis, S, Nakano, H & Cook, DN 2012, 'The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens', Nature Medicine, vol. 18, no. 11, pp. 1705-1710. https://doi.org/10.1038/nm.2920
Wilson RH, Maruoka S, Whitehead GS, Foley JF, Flake GP, Sever ML et al. The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens. Nature Medicine. 2012 Nov 1;18(11):1705-1710. https://doi.org/10.1038/nm.2920
Wilson, Rhonda H. ; Maruoka, Shuichiro ; Whitehead, Gregory S. ; Foley, Julie F. ; Flake, Gordon P. ; Sever, Michelle L. ; Zeldin, Darryl C. ; Kraft, Monica ; Garantziotis, Stavros ; Nakano, Hideki ; Cook, Donald N. / The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens. In: Nature Medicine. 2012 ; Vol. 18, No. 11. pp. 1705-1710.
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