title: A Toll-like receptor 2/6 agonist reduces allergic airway inflammation in chronic respiratory sensitisation to Timothy grass pollen antigens.
abstract: BACKGROUND
  The hygiene hypothesis negatively correlates the microbial burden of the environment with the prevalence of T helper type 2 (Th2)-related disorders, e.g. allergy and asthma. This is explained by Th1 triggering through pathogen-associated molecular patterns via Toll-like receptors (TLRs). In this study, the biological effects of a TLR2/6 agonist as a potential treatment of allergic inflammation are explored.
  
  
  METHODS
  In a model of chronic allergic airway inflammation induced by intranasal administration of Timothy grass pollen allergen extract, early TLR agonism and/or interferon (IFN)-gamma administration was compared to the therapeutic and immune-modulating effects of dexamethasone with regard to the cellular inflammation and cytokine profiles.
  
  
  RESULTS
  Eosinophilic inflammation was clearly reduced by TLR2/6 agonism. This effect was also seen without simultaneous administration of IFN-gamma. However, lymphocyte counts were not affected among the different treatment groups. More precise determination of the lymphocyte-mediated immune reaction showed that TLR2/6 agonism induced neither CD4+foxp3+ regulatory T cells in draining lymph nodes nor a pronounced Th1 immune response. In contrast, dexamethasone reduced both sensitisation as well as allergic inflammation and, in addition, CD11c+ antigen-presenting cells in lymph nodes. Our data clearly point to the potential to rebalance Th2-skewed allergic immune responses by therapeutic TLR2/6 agonist administration.
  
  
  CONCLUSIONS
  The use of the TLR2/6 agonist is a promising therapeutic approach in diseases with an imbalance in T cell responses, such as allergy and asthma.
authors.affiliation: Department of Immunology, Allergology and Immunotoxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fuchs
authors.forename: Saskia
authors.initials: S
authors.lastname: Knothe
authors.forename: Sabine
authors.initials: S
authors.lastname: Rochlitzer
authors.forename: Matthias
authors.initials: M
authors.lastname: Nassimi
authors.forename: Marina
authors.initials: M
authors.lastname: Greweling
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Lauenstein
authors.forename: Christina
authors.initials: C
authors.lastname: Nassenstein
authors.forename: Meike
authors.initials: M
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Ebensen
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Dittrich
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D039521:CD11c Antigen / Q000378:metabolism; D002452:Cell Count; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use; D015848:Interleukin-5 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D055666:Lipopeptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D031784:Phleum / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D011092:Polyethylene Glycols / Q000737:chemistry; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051216:Toll-Like Receptor 6 / Q000819:agonists*
chemical_list: D052179:Antigens, Plant; D039521:CD11c Antigen; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D015848:Interleukin-5; D055666:Lipopeptides; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D011092:Polyethylene Glycols; D003907:Dexamethasone; D007371:Interferon-gamma; C106335:macrophage stimulatory lipopeptide 2; D017493:Leukocyte Common Antigens