Autocrine Type I IFN Signaling in Dendritic Cells Stimulated with Fungal ?-Glucans or Lipopolysaccharide Promotes CD8 T Cell Activation.

ABSTRACT: Type I IFNs are key mediators of immune defense against viruses and bacteria. Type I IFNs were also previously implicated in protection against fungal infection, but their roles in antifungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal ?-glucans stimulate IFN-? production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of ?-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal ?-glucan particle-stimulated DCs. We demonstrate that ?-glucan-stimulated DCs induce CD8 T cell proliferation, activation marker (CD44 and CD69) expression, and production of IFN-?, IL-2, and granzyme B. Moreover, we show that type I IFNs support robust CD8 T cell activation (proliferation and IFN-? and granzyme B production) by ?-glucan-stimulated DCs in vitro and in vivo due to autocrine effects on the DCs. Specifically, type I IFNs promote Ag presentation on MHC I molecules, CD86 and CD40 expression, and the production of IL-12 p70, IL-2, IL-6, and TNF-? by ?-glucan-stimulated DCs. We also demonstrate a role for autocrine type I IFN signaling in bacterial LPS-induced DC maturation, although, in the context of LPS stimulation, this mechanism is not so critical for CD8 T cell activation (promotes IFN-? production but not proliferation or granzyme B production). This study provides insight into the mechanisms underlying CD8 T cell activation during infection, which may be useful in the rational design of vaccines directed against pathogens and tumors.

SUBMITTER: Hassanzadeh-Kiabi N 

PROVIDER: S-EPMC5173402 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature