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Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

PU.1 is involved in the immune response to Aspergillus fumigatus through upregulating Dectin-1 expression

Authors: Min Wang, Zhicheng Liu, Chenyang Liu, Ting Wu, Feng Cai, Quan Wang, Xin Su, Yi Shi

Published in: BMC Infectious Diseases | Issue 1/2016

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Abstract

Background

Invasive aspergillosis is a life-threatening disease, and its incidence has increased in the recent past. Dectin-1 recognizes β-glucans and mediates innate immune responses to Aspergillus fumigatus. Transcription factor PU.1 has been the focus of recent research due to its role in inflammation and infection. However, its role in Dectin-1 regulation during A. fumigatus infection remains to be elucidated.

Methods

THP-1 cells were stimulated with A. fumigatus conidia. We then used real-time RT-PCR, Western blot, and immunofluorescence assays to analyze the mRNA and protein levels and cellular distribution, respectively, of Dectin-1 and PU.1 in stimulated THP-1 cells. Additionally, we used the luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, electrophoretic mobility shift assays (EMSA), and RNA interference experiments to investigate the role of PU.1 in Dectin-1 regulation.

Results

Our results revealed that Dectin-1 mRNA and protein levels as well as the PU.1 protein level were increased in THP-1 cells stimulated with A. fumigatus conidia, while the mRNA expression level did not significantly change between the stimulated and control groups. We also observed that PU.1 translocated into the nucleus in stimulated THP-1 cells. The results of the luciferase reporter assay showed that PU.1 promoted human Dectin-1 (hDectin-1) gene activity. ChIP and EMSA indicated that PU.1 could bind with hDectin-1 gene promoter at three potential transcription factor-binding sites (TFBSs). In addition, knockdown of PU.1 significantly decreased Dectin-1 expression.

Conclusions

This study demonstrated the novel role of PU.1 in the immune response to A. fumigatus through upregulation of Dectin-1 expression and its translocation to the nucleus in A. fumigatus-stimulated THP-1 cells.
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Metadata
Title
PU.1 is involved in the immune response to Aspergillus fumigatus through upregulating Dectin-1 expression
Authors
Min Wang
Zhicheng Liu
Chenyang Liu
Ting Wu
Feng Cai
Quan Wang
Xin Su
Yi Shi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1632-x

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