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.

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells

“…In mice with allergic airway inflammation, dsRNA (a ligand of TLR3) challenge causes a significant exacerbation, increasing lung tissue inflammation score and tissue neutrophilia (37). TLR3 activation induces production of allergen-specific IgE and IgG1 (38). TLR3 null mice shows decreased rhinovirus-induced airway inflammatory and contractile responses (39).…”

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

“…In contrast, under certain circumstances such as the presence of certain danger signals, an orchestrated immune response develops including cells forming the innate (eg, macrophages, DCs, mast cells, innate lymphocytes) and the adaptive immune systems (T cells), and also of structural cells (eg, epithelial cells), which results in the development of specific T-and B-cell responses against the allergen. [28][29][30][31] In these sensitized individuals, exposure with the allergen results in specific immunological responses in the lung, in which mast cells and DCs modulate the adaptive immune responses, which is characterized by a Th2 response, including IL-4, IL-5, and IL-13, and accumulation of eosinophilic granulocytes in the airway wall and lumen. [32][33][34][35] If these immune responses persist in the airway wall, structural changes, such as goblet cell metaplasia, basement membrane thickening, hypertrophy of ASM, and subepithelial fibrosis, can occur and these structural changes are summarized under the term airway remodeling.…”

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

“…Therefore, airway plethysmography (Buxco Electronics) and bronchoalveolar lavage (BAL) were performed, and blood, thoracic lymph nodes, and lungs were isolated. From lymph nodes and the left lobe of the lung, singlecell suspensions were prepared, as described previously (29). Cells were investigated via FACS LSRII (BD Biosciences).…”