Human pDCs express the C-type Lectin receptor Dectin-1 and uptake and kill Aspergillus fumigatus spores in vitro (MPF4P.734)

Abstract

Abstract Plasmacytoid dendritic cells (pDCs) are the body’s most potent producers of type-1 IFNs, and are key responders to viruses like HIV, serving as an important link between the innate and adaptive immune responses. Although they are mainly anti-viral, evidence suggests pDCs also play an integral part in anti-fungal immunity. We demonstrated that human pDCs express the C-type Lectin receptor (CLR), Dectin-1, and that it is further upregulated after stimulation with HSV, Influenza, and the synthetic DNA ODN, CpG-A. In contrast, we did not find expression of Dectin-2, another CLR, on pDCs. Dectin-1 recognizes β-linked glucans, a component of the cell wall of opportunistic fungi like Aspergillus, Pneumocystis, and Candida, and is involved in immune functions including the uptake of fungi, induction of cytokine production, and direction of T-helper cell differentiation. Using Fluorescent Aspergillus Reporter (FLARE)-labelled A. fumigatus spores, which allow us to detect and differentiate between live and dead spores using flow cytometry, we showed that human pDCs can phagocytose and kill Aspergillus spores in vitro within a six-hour time frame. We hypothesize that Dectin-1 is the receptor responsible for this uptake. Although pDCs are classically considered IFN producers, stimulation with spores did not result in IFN-α production by pDC. Results from this ongoing study will shed further light on the role of human pDCs in anti-fungal immunity.