LAUSR

Aspergillus fumigatus (A. fumigatus) is one of the most common fungal pathogens of invasive pulmonary aspergillosis (IPA), which may be life threatening in immunocompromised individuals. The dendritic cell-associated C-type lectin receptor (Dectin-1), toll-like receptor (TLR)-2 and TLR-4 are major pattern recognition receptors in alveolar macrophages that recognize A. fumigatus components. The PU.1 transcription factor is known to be important for the transcriptional control of these three receptors in mature macrophages. The present study investigated whether alterations of PU.1 expression may affect the innate defense against A. fumigatus in the human monocyte THP-1 cell line. THP-1-derived macrophages were transduced with PU.1 adenoviral vectors and transfected with PU.1 small interfering RNA, and the mRNA and protein expression levels of Dectin-1, TLR-2 and TLR-4 were measured. In addition, the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were ascertained, and fungal phagocytosis and killing were assessed. The results demonstrated that overexpression of PU.1 by recombinant adenoviral vectors resulted in a significant upregulation of Dectin-1, TLR-2 and TLR-4 at the transcriptional and translational levels. In response to A. fumigatus stimulation, PU.1 overexpression increased TNF-α and IL-1β production. In addition, Dectin-1, TLR-2 and TLR-4 upregulation may have enhanced the phagocytosis and killing ability of THP-1-derived macrophages. As expected, silencing of PU.1 led to downregulation of Dectin-1, TLR-2, TLR-4 and the expression of pro-inflammatory cytokines, as well as decreased phagocytosis and the killing ability of THP1-derived macrophages. In conclusion, the results indicate that PU.1 may be a critical factor for the innate defense against A. fumigatus, and may therefore be a potential target for the prophylaxis and treatment of IPA.