title: Toll-like receptor (TLR) 7 decreases and TLR9 increases the airway responses in mice with established allergic inflammation.
abstract: Toll-like receptor (TLR) 7 and TLR9 recognise microbial products of viral descent. Since viruses are a common trigger of asthma exacerbations these TLRs have emerged as interesting therapeutic targets. Even though their effects on allergic inflammation have been evaluated in several models their effects on established allergic airway inflammation remains to be described. Therefore, mice with an on-going ovalbumin (OVA)-induced allergic airway inflammation were given R848 or CpG (TLR7 and TLR9 agonists, respectively) intranasally during four consecutive days. At day five, the R848 treatment had reduced OVA-induced airway hyperresponsiveness (measured as the increased resistance to methacholine), counteracted the accompanying influx of eosinophils and macrophages, and decreased the OVA-enhanced release of interleukin (IL)-5 and leukotriene (LT) B4 in bronchoalveolar lavage fluid. CpG, which by itself caused airway hyperresponsiveness, did not influence the OVA-induced airway hyperresponsiveness, and release of IL-5 and LTB4, but decreased the OVA-induced influx of cells in bronchoalveolar lavage fluid, and increased the amount of pro-inflammatory mediators like IL-12, CXCL1 and CXCL9. To conclude, TLR7 dampens the allergic airway reactivity and local inflammation, whereas TLR9 that causes airway hyperresponsiveness and increased cellular response per se, do generally not interfere with the effects induced by allergic inflammation.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden. Electronic address: mikael.adner@ki.se.
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.forename: Magnus
authors.initials: M
authors.lastname: Starkhammar
authors.forename: Susanna Kumlien
authors.initials: SK
authors.lastname: Georén
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Lars-Olaf
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D006967:Hypersensitivity / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
keywords: Airway mechanics; Allergy; Asthma; Innate immunity; Viral infection