PU.1 serves a critical role in the innate defense against Aspergillus fumigatus via dendritic cell-associated
C-type lectin receptor-1 and toll-like receptors-2 and 4 in THP-1-derived macrophages

Liu,Chenyang; Wang,Min; Sun,Wenkui; Cai,Feng; Geng,Shen; Su,Xin; Shi,Yi

doi:10.3892/mmr.2017.6504

PU.1 serves a critical role in the innate defense against Aspergillus fumigatus via dendritic cell-associated C-type lectin receptor-1 and toll-like receptors-2 and 4 in THP-1-derived macrophages

Authors:
- Chenyang Liu
- Min Wang
- Wenkui Sun
- Feng Cai
- Shen Geng
- Xin Su
- Yi Shi
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Affiliations: Graduate School, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai 200080, P.R. China, Department of Respiratory and Critical Care Medicine, Jinling Hospital Affiliated to Southern Medical University, Nanjing, Jiangsu 210002, P.R. China, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China
Published online on: April 24, 2017 https://doi.org/10.3892/mmr.2017.6504
Pages: 4084-4092
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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