Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model

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.

Lipopolysaccharide-Initiated Rhinosinusitis Causes Neuroinflammation and Olfactory Dysfunction in Mice

“…Many studies of rhinosinusitis animal models have reported the development of nasal polyps over a longer period. 13,14,33 Therefore, structural changes in the sinonasal mucosa may be at the microscopic level for this relatively short period of drug administration, and the major changes could be mainly observed at the molecular, cellular, and behavioral levels in our study.…”

IL‐17A facilitates type 2 inflammation in a modified eosinophilic chronic rhinosinusitis mouse model

“…injection with ovalbumin (OVA) or fungal extracts for 2 or 3 weeks, followed by nasal instillation with OVA or fungal extracts by irrigation or instillation for 8 or 12 weeks. 20,21 Significant EOS infiltration was observed in the nasal mucosa; however, no significant purulent secretion was found in the sinus cavity in these mouse models, which is the typical clinical characteristic of patients with ECRS. 22,23 Do-Yeon Cho et al inserted an aseptic synthetic sponge in the unilateral middle meatus of rabbits for 14 weeks to construct a CRS model that showed clear purulent secretions in the middle meatus, and inflammatory cells infiltrated into the epithelium and subepithelial space, subepithelial edema, and epithelial hypertrophy.…”

“…In current studies, ECRS mouse models are mainly induced by intraperitoneal (i.p.) injection with ovalbumin (OVA) or fungal extracts for 2 or 3 weeks, followed by nasal instillation with OVA or fungal extracts by irrigation or instillation for 8 or 12 weeks 20,21 . Significant EOS infiltration was observed in the nasal mucosa; however, no significant purulent secretion was found in the sinus cavity in these mouse models, which is the typical clinical characteristic of patients with ECRS 22,23 .…”

Alternaria as an Inducer of Allergic Sensitization

“…Asthma and respiratory allergy are two diseases that are still not fully understood, with several unrelated explanations for the mechanisms of how a patient acquires these phenotypes. However, numerous studies have reported a strong correlation between Alternaria inhalation and the development of asthma or allergic rhinitis [ 66 , 67 , 68 , 69 ].…”