title: Dectin-1 is inducible and plays a crucial role in Aspergillus-induced innate immune responses in human bronchial epithelial cells.
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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing 210002, China.
authors.forename: W-K
authors.initials: WK
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: Q-Y
authors.initials: QY
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: H-M
authors.initials: HM
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology*; D001980:Bronchi / Q000276:immunology* / Q000382:microbiology; D001985:Bronchial Provocation Tests; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005936:Glucans; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008856:Microscopy, Fluorescence; D011134:Polysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013172:Spores, Fungal / Q000276:immunology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D005936:Glucans; D016209:Interleukin-8; D037181:Lectins, C-Type; D011134:Polysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C546929:CLEC7A protein, human; D000099181:Dectin-1; C508606:CXCL8 protein, human; C526629:DEFB-109 peptide, human; C495342:TLR2 protein, human; C008247:laminaran