Co-stimulation of TLR4 and Dectin-1 Induces the Production of Inflammatory Cytokines but not TGF-? for Th17 Cell Differentiation.

ABSTRACT: Collaboration of TLR and non-TLR pathways in innate immune cells, which acts in concert for the induction of inflammatory cytokines, can mount a specific adaptive immune response tailored to a pathogen. Here, we show that murine DC produced increased IL-23 and IL-6 when they were treated with LPS together with curdlan that activates TLR4 and dectin-1, respectively. We also found that the induction of the inflammatory cytokine production by LPS and curdlan requires activation of IKK. However, the same treatment did not induce DC to produce a sufficient amount of TGF-?. As a result, the conditioned media from DC treated with LPS and curdlan was not able to direct CD4(+) T cells to Th17 cells. Addition of TGF-? but not IL-6 or IL-1? was able to promote IL-17 production from CD4(+) T cells. Our results showed that although signaling mediated by LPS together with curdlan is a potent stimulator of DC to secrete many pro-inflammatory cytokines, TGF-? production is a limiting factor for promoting Th17 immunity.

SUBMITTER: Chang J 

PROVIDER: S-EPMC3942505 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature