Introduction: Plasmacytoid Dendritic Cells (pDC) are a subset of dendritic cells that play an important role in antiviral immunity, and recent evidence indicates a lesser-known role in antifungal immunity. Here, we characterize the details and mechanisms of the pDC response to Aspergillus fumigatus (AF) conidia.
Methods: Conidia were labeled with Fluorescent Aspergillus Reporter, comprised of a viability and tracker dye, and observed under confocal microscopy and imaging flow cytometry after co-incubation with purified pDCs from a healthy donor. We used flow cytometry to evaluate pDC expression of pattern recognition receptors (PRR) on pDCs from various tissues, including healthy and HIV-infected peripheral blood, bone marrow, cord blood, and tonsils. We then measured pDC activation/maturation in response to the specific Dectin-1 agonist curdlan and AF conidia.
Results: Human pDCs did not strongly phagocytose conidia, but instead bound them tightly to the cell surface. PRRs expressed by pDCs included Dectin-1 and Mannose Receptor (MR), but not Dectin-2. Dectin-1 was detected on all tissue types, and was up-regulated in response to several stimulants including curdlan and HSV. Dectin-1 was expressed to a higher degree on pDCs from HIV-infected individuals than in healthy controls. Curdlan stimulation induced a dose-responsive up-regulation of pDC activation/maturation markers CD40, CD80, CD83, and CD86, and the production of IL-6. Stimulation with AF induced the up-regulation of CD40, CD86, MHC-I, and HLA-DR, as well as the down-regulation of CD62L and CXCR3. Activation/maturation in response to AF was slower, but as strong as their viral response. Notably, neither AF nor curdlan stimulation induced pDC IFN-α production.
Conclusion: Exposure to AF conidia induces human pDC activation and maturation, and the expression and functionality of Dectin-1 on pDCs represents a possible route for the induction of this pDC response. Together, these results shed light on how pDCs recognize and respond to fungal infection.