Abstract
Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.
Highlights
Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of diseases that can be classified as eosinophilic or non-eosinophilic CRS based on the dominant inflammatory cell types
Repeated intranasal instillation of Alternaria elevated the level of IL-4, IL-10, and tumor necrosis factor (TNF)-α in nasal lavage fluid (NLF) of allergic CRS mice at 8 (IL-4, 19.4 ± 9.6 pg/mL; IL-10, 2.6 ± 2.3 pg/mL; TNF-α, 7.9 ± 5.9 pg/mL) and 16 weeks (IL-4, 19.1 ± 5.9 pg/mL; IL-10, 3.5 ± 1.7 pg/mL; TNF-α, 8.5 ± 5.2 pg/ mL)
When the mice were treated with Alternaria for 8 and 16 weeks, eosinophil and neutrophil counts were significantly increased in NLF of non-allergic CRS mice
Summary
Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of diseases that can be classified as eosinophilic or non-eosinophilic CRS based on the dominant inflammatory cell types. Alternaria chronic rhinosinusitis model are not fully understood, CRS is characterized by the chronic inflammation of sinonasal mucosa with a heterogeneous group of inflammatory responses against allergens, bacteria, fungi, and viruses. [2] Fungi are increasingly recognized as important pathogens in patients with sinusitis; their role in the pathogenesis of CRS remains controversial. Fungal components, such as proteins and enzymes, induce immune responses and result in the production of chemical mediators through the interaction of cell membrane receptors. [3, 4] Alternaria and Aspergillus extracts activate upper and lower airway epithelial cells and enhances the production of several inflammatory mediators; they are considered risk factors for the development of asthma, allergic rhinitis, and CRS. Fungal components, such as proteins and enzymes, induce immune responses and result in the production of chemical mediators through the interaction of cell membrane receptors. [3, 4] Alternaria and Aspergillus extracts activate upper and lower airway epithelial cells and enhances the production of several inflammatory mediators; they are considered risk factors for the development of asthma, allergic rhinitis, and CRS. [5,6,7,8]
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