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.

Dectin-1 Is Not Required for Controlling Candida albicans Colonization of the Gastrointestinal Tract

“…However, dectin-1 expression can be induced in epithelial tissues (25), and this receptor may play a role under certain inflammatory conditions, such as we have recently shown during colitis (14).…”

The mtfA Transcription Factor Gene Controls Morphogenesis, Gliotoxin Production, and Virulence in the Opportunistic Human Pathogen Aspergillus fumigatus

“…The first point of contact is with the bronchial epithelial cells (1). These cells have dectin-1 receptors that can recognize the ␤-1,3-glucan on the cell surfaces of conidia (1,13,14), activating the production of reactive oxygen species (ROS) and of antimicrobial peptides and cytokines as part of the initial immune response. In healthy individuals, conidia that are able to evade mucociliary clearance are quickly removed by either alveolar macrophages or epithelial cells via phagocytosis.…”

On the evolution of azole resistance in Aspergillus fumigatus

“…59 In addition, effectors of the innate immunity such as antimicrobial peptides, which are induced in bronchial epithelial cells in response to A. fumigatus, exhibit antifungal activity. 60 Adaptation through biofilm formation or possibly antimicrobial-peptide-resistance mutations will further enable the fungus to persist in the host.…”