TLR3 but not TLR7/8 ligand induces allergic sensitization to inhaled allergen.

Abstract

Epidemiological studies suggest that viral infections during childhood are a risk factor for the development of asthma. However, the role of virus-specific pattern recognition receptors in this process is not well defined. In the current study, we compare the effects of the inhaled viral TLR ligands polyinosinic-polycytidylic acid (TLR3) and resiquimod (TLR7/8) on sensitization to a model allergen (OVA) in a murine model. Both compounds enhance the migration, activation, and Ag-processing of myeloid dendritic cells from the lung to the draining lymph nodes comparable to the effects of LPS. Application of polyinosinic-polycytidylic acid [poly(I:C)] or LPS induces production of allergen-specific IgE and IgG1, whereas resiquimod (R848) had no effect. In addition, rechallenge of mice with OVA resulted in airway inflammation and mucus production in animals that received either poly(I:C) or LPS but not after application of R848. In summary, these results show that activation of TLR3 in combination with inhaled allergen results in induction of dendritic cell activation and migration similar to the effects of LPS. This leads to the development of allergic airway disease after allergen rechallenge, whereas mice treated with R848 did not develop allergic airway disease. These findings give further insight into the effects of stimulation of different TLRs on the development of asthma.

• Authors: Sebastian Reuter, Nina Dehzad, Helen Martin, Livia Böhm, Marc Becker, Roland Buhl, Michael Stassen, Christian Taube
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 10 Pg. 5123-31 (May 15 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22491246 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Imidazoles
• Ligands
• Lipopolysaccharides
• Membrane Glycoproteins
• TLR3 protein, mouse
• TLR8 protein, mouse
• Tlr7 protein, mouse
• Toll-Like Receptor 3
• Toll-Like Receptor 7
• Toll-Like Receptor 8
• Ovalbumin
• Poly I-C
• resiquimod

Topics

• Administration, Inhalation
• Allergens (administration & dosage, immunology)
• Animals
• Dendritic Cells (immunology, metabolism)
• Disease Models, Animal
• Hypersensitivity (immunology, microbiology, virology)
• Imidazoles (administration & dosage, metabolism)
• Ligands
• Lipopolysaccharides (administration & dosage, metabolism)
• Membrane Glycoproteins (agonists, deficiency, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Ovalbumin (administration & dosage, immunology)
• Poly I-C (administration & dosage, metabolism)
• Toll-Like Receptor 3 (deficiency, metabolism)
• Toll-Like Receptor 7 (agonists, deficiency, metabolism)
• Toll-Like Receptor 8 (agonists, metabolism)