Background: Invasive aspergillosis is a life-threatening disease, and its incidence has increased in the recent past.\nDectin-1 recognizes �²-glucans and mediates innate immune responses to Aspergillus fumigatus. Transcription factor\nPU.1 has been the focus of recent research due to its role in inflammation and infection. However, its role in\nDectin-1 regulation during A. fumigatus infection remains to be elucidated.\nMethods: THP-1 cells were stimulated with A. fumigatus conidia. We then used real-time RT-PCR, Western blot, and\nimmunofluorescence assays to analyze the mRNA and protein levels and cellular distribution, respectively, of Dectin-1\nand PU.1 in stimulated THP-1 cells. Additionally, we used the luciferase reporter assays, chromatin immunoprecipitation\n(ChIP) assays, electrophoretic mobility shift assays (EMSA), and RNA interference experiments to investigate the role of\nPU.1 in Dectin-1 regulation.\nResults: Our results revealed that Dectin-1 mRNA and protein levels as well as the PU.1 protein level were increased in\nTHP-1 cells stimulated with A. fumigatus conidia, while the mRNA expression level did not significantly change between\nthe stimulated and control groups. We also observed that PU.1 translocated into the nucleus in stimulated THP-1 cells.\nThe results of the luciferase reporter assay showed that PU.1 promoted human Dectin-1 (hDectin-1) gene activity. ChIP\nand EMSA indicated that PU.1 could bind with hDectin-1 gene promoter at three potential transcription factor-binding\nsites (TFBSs). In addition, knockdown of PU.1 significantly decreased Dectin-1 expression.\nConclusions: This study demonstrated the novel role of PU.1 in the immune response to A. fumigatus through\nupregulation of Dectin-1 expression and its translocation to the nucleus in A. fumigatus-stimulated THP-1 cells.
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