Abstract
BACKGROUND: Immunosuppression is believed to increase the risk of invasive pulmonary aspergillosis (IPA), but information on the mechanism is limited. Therefore, we analyze the effect and mechanism of the pathogenesis and disease progression of IPA in a combined immunosuppressed rat model. METHODS: The immunosuppressed rat model was established by intraperitoneal injection of cyclophosphamide (CTX) and dexamethasone (DXM). IPA was established by nasal inoculation of Aspergillus fumigatus spore suspension. Pathological sections and tissue homogenate culture were used to evaluate the lung tissue. Routine blood and inflammatory indexes were dynamically observed. The expressions of NLRP3/caspase-1/GSDMD protein and gene were determined using western blot and quantitative polymerase chain reaction (q-PCR) respectively. T-test or one-way repeated measures analysis were used to do statistical analysis on the groups. RESULTS: Following intraperitoneal of CTX and DXM injections, the rats showed depression, weight loss, and significant decreases in the numbers of leukocytes and classified cells. Pathological sections revealed more severe lung lesions in the immunosuppressed rats infected with Aspergillus fumigatus. The expression of NLRP3/caspase-1/GSDMD protein increased significantly in both the aspergillosis and immunosuppressed plus aspergillosis groups. CONCLUSIONS: The pathological development of IPA in the immunosuppressed rats had the most serious effects, and the findings strongly implicated NLRP3/caspase-1/GSDMD pathway involvement.