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.
Conclusion:
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.
Copyright 2009 S. Karger AG, Basel.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, Plant / administration & dosage
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Antigens, Plant / immunology*
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / cytology
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CD11c Antigen / metabolism
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Cell Count
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Chemokines / metabolism
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Cytokines / metabolism
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Dexamethasone / pharmacology
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Dexamethasone / therapeutic use
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Female
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Immunization
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Immunoglobulin G / blood
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Immunoglobulin G / immunology
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation / pathology
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Inflammation / prevention & control
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Interferon-gamma / pharmacology
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Interferon-gamma / therapeutic use
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Interleukin-5 / metabolism
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Leukocyte Common Antigens / metabolism
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Lipopeptides / chemistry
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Lipopeptides / pharmacology
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Lipopeptides / therapeutic use*
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Lung / drug effects
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Lymph Nodes / cytology
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Lymph Nodes / drug effects
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Lymph Nodes / immunology
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Mice
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Mice, Inbred BALB C
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Phleum / immunology*
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Pollen / immunology*
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Polyethylene Glycols / chemistry
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Respiratory Hypersensitivity / immunology
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Respiratory Hypersensitivity / metabolism
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Respiratory Hypersensitivity / pathology
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Respiratory Hypersensitivity / prevention & control*
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Spleen / cytology
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Spleen / drug effects
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Spleen / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Toll-Like Receptor 2 / agonists*
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Toll-Like Receptor 6 / agonists*
Substances
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Antigens, Plant
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CD11c Antigen
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Chemokines
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Cytokines
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Immunoglobulin G
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Interleukin-5
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Lipopeptides
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Tlr2 protein, mouse
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Tlr6 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 6
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Polyethylene Glycols
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Dexamethasone
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Interferon-gamma
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macrophage stimulatory lipopeptide 2
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Leukocyte Common Antigens