BackgroundAcute 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.MethodsSprague–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 × 107 conidia/ml in group A, 107 conidia/ml in group B, and 106 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.ResultsAn 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0713-y) contains supplementary material, which is available to authorized users.
Fungal rhinosinusitis (FRS) is commonly caused by various Aspergillus species (spp) and Mucorales fungi, and the treatment and prognosis of cases differ depending on the causative fungus. The present study describes a novel immunohistochemical method that has high sensitivity and specificity for distinguishing between these two types of fungi in patients with FRS. Three groups were included in the study. Group A included formalin-fixed paraffin-embedded blocks of 51 nasal tissue specimens of patients with FRS (27 Aspergillus spp and 24 Mucorales) that were continuously obtained from the Department of Pathology of Tongren Hospital in Beijing as the experimental group and 34 cultures (26 Aspergillus spp and 8 Mucorales) of FRS that were randomly selected from the bacterial laboratory of Tongren Hospital in Beijing to verify the staining results of the paraffin-embedded blocks. Formalin-fixed paraffin-embedded blocks of 10 esophageal cancer specimens were included in Group B as the positive control group. All specimens in Groups A and B were stained with interferon-γ (IFN-γ) antibody. Group C consisted of the same specimens as described in Group A, however, when performing the immunohistochemical assay, IFN-γ antibody was replaced by PBS and this served as the negative control group. The differences in IFN-γ immunohistochemical staining between Aspergillus spp and Mucorales were analyzed. Staining of IFN-γ in paraffin-embedded samples was positive in 92.6% (25/27) of specimens in which Aspergillus spp were the causative pathogen, which was significantly higher compared with specimens in which Mucorales was causative (P<0.001), with only 4.2% (1/24) of specimens staining positive for IFN-γ. Immunohistochemical staining of cell cultures was 100% positive for Aspergillus spp, whereas all Mucorales were negative. Thus, the results of the current study indicated that IFN-γ antibody immunohistochemical staining may be used as a novel diagnostic tool to distinguish between Aspergillus spp and Mucorales when identifying the causative agent in FRS, providing a useful supplementary test to the current immunohistochemical methods in the clinical diagnosis of FRS.
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