A Toll-like receptor 2/6 agonist reduces allergic airway inflammation in chronic respiratory sensitisation to Timothy grass pollen antigens.
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.
Fuchs
Barbara
B
Department of Immunology, Allergology and Immunotoxicology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
Knothe
Saskia
S
Rochlitzer
Sabine
S
Nassimi
Matthias
M
Greweling
Marina
M
Lauenstein
Hans-Dieter
HD
Nassenstein
Christina
C
Müller
Meike
M
Ebensen
Thomas
T
Dittrich
Anna-Maria
AM
Krug
Norbert
N
Guzman
Carlos A
CA
Braun
Armin
A
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*
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