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Dectin-1 is inducible and plays a crucial role in Aspergillus-induced innate immune responses in human bronchial epithelial cells

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Abstract

Airway epithelial cells are the first cells to be challenged upon contact with the conidia of Aspergillus. In response, they express pattern-recognition receptors that play fundamental roles as sentinels and mediators of pulmonary innate immunity. The C-type lectin Dectin-1 is expressed predominantly on the surface of myeloid lineage cells. We examined the induction, regulation, and functions of Dectin-1 in pulmonary epithelial cells by challenging human bronchial epithelial (HBE) cells with A. fumigatus. Inflammatory, antimicrobial peptide genes and reactive oxygen species (ROS) were quantified, with and without knockdown of Dectin-1. We found that A. fumigatus induced the expression of Dectin-1 mRNA and protein in HBE cells in a toll-like receptor (TLR) 2-dependent manner. In addition, A. fumigatus-mediated generation of ROS was dependent on the upregulation of Dectin-1. Moreover, A. fumigatus actively induced the expression of TNFα, GM-CSF, IL8, HBD2, and HBD9. Knockdown of Dectin-1 inhibited TNFα, IL8, HBD2, and HBD9 expression. Hence, Dectin-1 was required for the upregulation of pro-inflammatory cytokines and antimicrobial peptides. Finally, knockdown of TLR2 significantly inhibited Dectin-1 upregulation. Our results demonstrate the novel induction of Dectin-1 in human bronchial epithelial cells and its critical role in the innate immune response against A. fumigatus in non-phagocytic cells.

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Acknowledgments

This study was granted by the Hospital Foundation of Jinling Hospital (2011026). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing, 210002, China

    W.-K. Sun, X. Su, Y. Song, H.-M. Sun & Y. Shi

  2. Nanjing University School of Medicine, Nanjing, China

    X. Lu, X. Li & Q.-Y. Sun

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  1. W.-K. Sun
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  2. X. Lu
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  4. Q.-Y. Sun
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Correspondence to Y. Shi.

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Table 1

Sequences of primers for the real-time polymerase chain reaction (PCR) (DOCX 12 kb)

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Sun, WK., Lu, X., Li, X. et al. Dectin-1 is inducible and plays a crucial role in Aspergillus-induced innate immune responses in human bronchial epithelial cells. Eur J Clin Microbiol Infect Dis 31, 2755–2764 (2012). https://doi.org/10.1007/s10096-012-1624-8

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  • DOI: https://doi.org/10.1007/s10096-012-1624-8

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