title: A novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study.
abstract: BACKGROUND
  Acute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. Knowledge about this disease is still limited due to the scarcity of animal models designed to study the pathogenesis of this infection. Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. Therefore, the objectives of this study were to create a rat model of acute invasive fungal rhinosinusitis based on analyzing the impact of different fungal concentrations on establishing infection, and to observe the changes of mast cells in rats with this disease.
  
  
  METHODS
  Sprague-Dawley rats were divided randomly into four groups, three of which were experimental and received different concentrations of Aspergillus fumigatus inoculations, and one was a control group (D). The inoculated Aspergillus fumigatus concentrations were 5 × 10(7) conidia/ml in group A, 10(7) conidia/ml in group B, and 10(6) conidia/ml in group C. Before fungal inoculation, rats were immunosuppressed using cyclophosphamide and cortisone acetate, and had Merocel sponges inserted into the right nares. Hematology and histopathology investigations were then performed.
  
  
  RESULTS
  An acute invasive fungal rhinosinusitis rat model was established successfully with an incidence rate of 90% in group A, 50% in group B and 10% in group C. Aspergillus fumigatus invasion was observed in 20% of the lungs in group A, but was not seen in the remaining groups. In addition, no fungi invaded the orbital tissue, brains, livers, spleens or kidneys of any rat. Compared with the control set, the total number of mast cells in the experimental groups was not significantly increased, but mast cell degranulation, on the other hand, was only found in infected nasal cavities.
  
  
  CONCLUSIONS
  This investigation illustrates that various fungal concentrations have different effects on the incidence of acute invasive fungal rhinosinusitis, and it also demonstrates the feasibility of using this model to study the process of fungal rhinosinusoidal invasion. In addition, the results suggest that mast cells may play a role in the protection of sinuses against acute Aspergillus fumigatus infection and in the clearance of established hyphal masses.
authors.affiliation: Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. yanyuyan20061979@126.com.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Dermatology, First Hospital, Peking University, Beijing, 100034, People's Republic of China. zhaozuotaotao@163.com.
authors.forename: Zuotao
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. 120756849@qq.com.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. dw8812@163.com.
authors.forename: Ruochen
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of ENT, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. fangjugao@163.com.
authors.forename: Jugao
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Pathology, Affiliated Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. 18931107350ab@sina.com.
authors.forename: Honggang
authors.initials: H
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus; D004195:Disease Models, Animal; D007108:Immune Tolerance; D016867:Immunocompromised Host; D008168:Lung / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012220:Rhinitis / Q000276:immunology* / Q000382:microbiology; D012852:Sinusitis / Q000276:immunology* / Q000382:microbiology; D013172:Spores, Fungal