Increased susceptibility of irradiated mice to Aspergillus fumigatus infection via NLRP3/GSDMD pathway in pulmonary bronchial epithelia

• DOI: 10.1186/s12964-022-00907-2
• Publication Date: 2022-06-27T21:03:57Z
• Authors: Dong-Ming Wu; Miao He; Yang-Yang Zhao; Shi-Hua Deng; Teng Liu; Ting Zhang; Feng Zhang; Yuan-Yi Wang; Ying Xu
• Keywords: Pyroptosis

Abstract Background Aspergillus fumigatus infection is difficult to diagnose clinically and can develop into invasive pulmonary aspergillosis, which has a high fatality rate. The incidence of increased die widespread application radiotherapy technology. However, knowledge regarding A. following radiation exposure limited, the underlying mechanism remains unclear. In this study, we established mouse model explore effect on associated mechanisms. Methods after was by irradiating with 5 Gy chest instilling × 10 7 /ml conidia trachea 24 h study its function mechanism. Mice were compared among groups: normal controls (CON), only (RA), (Af), + (RA Af). Staining analyses used detect damage in lung tissues. Changes protein mRNA levels pyroptosis-related molecules assessed western blot analysis quantitative reverse transcription polymerase chain reaction, respectively. Protein concentrations serum alveolar lavage fluid also measured. An immunofluorescence colocalization performed confirm that NLRP3 inflammasomes activated pyroptosis. Results Radiation destroyed epithelial barrier significantly fungal burden . active end caspase-1 gasdermin D (GSDMD) highly expressed even infection. Release interleukin-18 (IL-18) interleukin-1β (IL-1β) provided further evidence knockout inhibited pyroptosis, effectively attenuated reduced Conclusions Our findings indicated activation susceptibility Due pyroptosis cells, it resulted destruction tissue. Moreover, found reducing damage. Overall, our results suggest NLRP3/GSDMD pathway mediated-pyroptosis lungs may be key event process provide new insights