Nasal Sensitization with Ragweed Pollen Induces Local-Allergic-Rhinitis-Like Symptoms in Mice

Abstract

Recently, the concept of local allergic rhinitis (LAR) was established, namely rhinitis symptoms with local IgE production and negative serum antigen-specific IgE. However, the natural course of LAR development and the disease pathogenesis is poorly understood. This study investigated the pathophysiology of mice with allergic rhinitis that initially sensitized with ragweed pollen through the nasal route. Mice were nasally administrated ragweed pollen over consecutive days without prior systemic immunization of the allergen. Serial nasal sensitization of ragweed pollen induced an allergen-specific increase in sneezing, eosinophilic infiltration, and the production of local IgE by day 7, but serum antigen-specific IgE was not detected. Th2 cells accumulated in nose and cervical lymph nodes as early as day 3. These symptoms are characteristic of human LAR. Continual nasal exposure of ragweed pollen for 3 weeks resulted in the onset of classical AR with systemic atopy and adversely affected lung inflammation when the allergen was instilled into the lung. Fcer1a −/− mice were defective in sneezing but developed normal eosinophilic infiltration. Contrary, Rag2 −/− mice were defective in both sneezing and eosinophilic infiltration, suggesting that T cells play a central role in the pathogenesis of the disease. These observations demonstrate nasal allergen sensitization to non-atopic individuals can induce LAR. Because local Th2 cell accumulation is the first sign and Th2 cells have a central role in the disease, a T-cell-based approach may aid the diagnosis and treatment of LAR.

Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier

“…DEP disrupted the TJs between nasal epithelial cells and increased paracellular permeability of the epithelium. However, the current study used ragweed pollen, which has intrinsic adjuvant activity and does not require other adjuvants for nasal sensitization [27]. DEP exacerbated sneezing in mice with ragweed-pollen-specific AR.…”

“…The production of Th2 cytokines, IL-4, IL-5, and IL-13, from cLN cells by in vitro restimulation with ragweed antigen was comparable between ragweed-alone-challenged and ragweed-plus-DEP-challenged groups (Fig. Numbers of eosinophils in the nasal mucosa, which represent late-phase responses of AR and are largely dependent on Th2 cell activation [19,27], were similar between the groups (Fig. Numbers of eosinophils in the nasal mucosa, which represent late-phase responses of AR and are largely dependent on Th2 cell activation [19,27], were similar between the groups (Fig.…”

Allergen endotoxins induce T-cell–dependent and non–IgE-mediated nasal hypersensitivity in mice

“…WT and Fcer1a 2/2 mice, deficient for FcεRI and thus deficient for IgE-mediated allergic reactions, 9,37 were i.p. immunized with Ef-OVA 3 times (days 218, 211, and 24), then i.n.…”

“…AR diagnosis is based on rhinitis symptoms: sneezing, nasal discharge, and nasal clotting, and the presence of systemic or local (nasal) allergen-specific IgE. [8][9][10] Patients with rhinitis without allergen-specific IgE are diagnosed as suffering from nonallergic rhinitis (NAR) and, in most cases, triggers of the symptoms are unclear. 11 Although NAR is not considered an allergy, some patients with NAR show nasal infiltration of inflammatory cells including neutrophils, eosinophils, and mast cells that suggests local activation of innate and/or adaptive immunity.…”

Vaccine development and new attempts of treatment for ragweed allergy

“…Kato and colleagues investigated the pathophysiology of mice with allergic rhinitis that initially sensitized with ragweed pollen through the nasal route [Kato et al 2014]. The results demonstrated that nasal sensitization with an allergen induced systemic atopy, which can adversely affect the onset of other allergic diseases when the individuals encounter the same allergen.…”