Abstract:

BACKGROUND: Pulmonary aspergillosis is a disease caused by pulmonary fungal infection. Its diagnosis and treatment is usually delayed because of nonspecific clinical symptoms, physicial sign and imaging changes as well as uncertainties of histological and bacterial findings. Therefore, it is necessary to establish mouse models of invasive pulmonary aspergillosis to investigate the underlying pathological mechanism and novel therapeutic methods.
OBJECTIVE: To establish mouse models of invasive pulmonary aspergillosis, detect the expression of 
γ-interferon, Toll-like receptor 2 and Toll-like receptor 4, and discuss the mechanism of action underlying invasive pulmonary aspergillosis.
METHODS: Seventy-five female BALB/c mice of clean grade, aged 6-8 weeks, were randomly and evenly divided into five groups: blank control group (group A), immunosuppressive model group treated with high concentrations of Aspergillus fumigatus spore suspension (group B), normal infection group treated with high concentration of Aspergillus fumigatus spore suspension (group C), immunosuppressive model group treated with low concentration of Aspergillus fumigatus spore suspension (group D), normal infection group treated with low concentration of Aspergillus fumigatus spore suspension (group E). First, mice in the groups B and D were intraperitoneally injected with cyclophosphamide to establish immunosuppressive models. The mice in the groups D, E (108 cfu/mL) and groups B, C (109 cfu/mL) were treated with 12 mL Aspergillus fumigatus spore suspension through the use of nebulizer. Mice in the group A were treated identically with sterile PBS. At 1, 3, 5 days of infection, the pathological change of lung tissue was observed, the mass concentration of γ-interferon in bronchoalveolar lavage fluid and the expression levels of γ-interferon mRNA and Toll-like receptor 2 and Toll-like receptor 4 mRNA and protein in the lung tissue were determined.
RESULTS AND CONCLUSION: Abscess, spores and very severe bleeding and congestion, widenened alveolar septum and tracheal epithelial cell shedding and necrosis were observed in the mouse lung tissue in the group B. At 5 days of infection, the mass concentration of γ-interferon in bronchoalveolar lavage fluid and the expression of γ-interferon mRNA in the lung tissue in the group B were significantly decreased compared with the group A (P < 0.05). Toll-like receptor 2 expression was strongly positive in the group B. Toll-like receptor 2 expression in the group C was significantly lower than that in the group B (P < 0.05). Toll-like receptor 4 expression was positive in the groups B and C, and its expression in the group C was significantly greater than in the group B (P < 0.05). The expression of Toll-like receptor 2, 4 mRNA in the mouse lung tissue of group B was significantly increased at 1, 3, 5 days of infection (P < 0.05). These results suggest that atomizing high concentration of aspergillus fumigatus spore suspension to immunosuppressive mice can establish stable invasive pulmonary aspergillosis models with typical pathological features. The infection of aspergillus fumigatus can activate toll-like receptor 2, 4 at the same time, and the pathological mechanism is closely related to organism’s immune defense function. 

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Key words: Invasive Pulmonary Aspergillosis, Model, Animal, Interferon γ, Toll-like Receptor