Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling

Allergic asthma is a serious multifaceted disease characterized by eosinophil-rich airway inflammation, airway hyperreactivity and airway wall modifications known as remodelling. We previously demonstrated that the spores of two allergenic moulds, Alternaria alternata and Cladosporium herbarum, were potent inducers of immunoglobulin E (IgE) production. Moreover, mice sensitized by two intraperitoneal injections before intranasal challenge with A. alternata or C. herbarum spores developed an allergic lung inflammation and hyperreactivity. Here we report on the effect of chronic intranasal administration of C. herbarum spores or A. alternata extracts to unsensitized BALB/c mice. Our results demonstrate that this chronic treatment led to an increase of total serum IgE and the appearance of specific IgE and IgG1. Total cell number in bronchoalveolar lavage fluid from treated mice was highly increased compared to phosphate-buffered-saline-treated mice because of the accumulation of macrophages, neutrophils, lymphocytes and eosinophils. Airway hyperreactivity appeared after 3 weeks (extract) and 7 weeks (spores) and was maintained during the whole treatment. Increased interleukin-13 mRNA expression in the lungs and T helper type 2 cytokines (interleukin-4, -5, -6 and -13) and transforming growth factor-β secretion in bronchoalveolar lavage fluid were also observed. Lung hydroxyproline and fibronectin contents indicated increased fibrosis in mice treated with mould allergen. These observations were confirmed by histological analysis demonstrating airway wall remodelling and strong mucus production. These observations show that this model, using chronic intranasal administration of relevant particulate allergens, is an interesting tool for the study of mechanisms leading to allergic pulmonary diseases and lung remodelling