pDCs are important components of the immune response to viruses but their contribution to host defenses against fungal infections is unclear. Previously, we demonstrated that A. fumigatus DNA stimulates secretion of type I IFN by human pDCs. Here, we examined the interactions of human pDCs, isolated from the peripheral blood by selection of CD304+ cells, with live A. fumigatus hyphae. Microscopic observations revealed that following in vitro co-incubation, pDCs closely associate with A. fumigatus hyphae. Furthermore, pDCs had potent activity against A. fumigatus, with up to 80% inhibition of hyphal metabolic activity or growth as assayed by an XTT reduction assay. Growth inhibition of A. fumigatus by pDCs was also seen when hyphal lengths were measured by light microscopy. Antifungal activity appeared to be mediated, at least in part, by preformed factors as similar activity was observed when A. fumigatus was incubated with pDC lysates compared with intact pDCs. Finally, pDCs secreted the proinflammatory cytokines TNFα and IFNα in response to stimulation by A. fumigatus hyphae. Together these data suggest that pDCs may be contributing to the antifungal response by inhibiting fungal growth and communicating with other cell types via the secretion of cytokines.
Full conference title:
110th General Meeting American Society for Microbiology
- ASM 110th (2010)