The TLR5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens

Article (PDF Available)inNature medicine 18(11) · October 2012with40 Reads
DOI: 10.1038/nm.2920 · Source: PubMed
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.


    • "Schülke et al. [70, 71] reported that intraperitoneal administration of fl agellin–ovalbumin fusion protein prevented intestinal allergy in mice. On the other hand, Wilson et al. [72] instilled fl agellin together with ovalbumin into the airways of mice in which it induced strong allergic airway responses to ovalbumin. They also found high titers of antifl agellin antibody in sera of asthmatics. "
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    • "For example treatment of BALB/c mice, intranasally sensitized to the chicken egg white allergen Ova, with a mixture of V. vulnificus flagellin B and Ova significantly inhibited subsequent Ova-induced airway hyperreactivity, airway inflammation, and TH2-cytokine production [7]. In contrast, in vivo Salmonella flagellin C application stimulated strong TLR5 dependent allergic airway responses to inhaled Ova and primed allergic responses to natural indoor allergens present in house dust extracts [8]. "
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    • "DC-SIGN can recognize diverse allergens as well, however, leading to a Th1 polarization. Finally, TLR5 can be activated by HDM extracts containing flagellin (34). "
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