Interactions between the NLRP3-Dependent IL-1 beta and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

Generally, a reciprocal antagonistic interaction exists between the antiviral type I interferon (IFN) and the antibacterial nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)-dependent IL-1 beta pathways that can significantly shape immune responses. Plasmacytoid dendritic cells (pDCs), as professional type I IFN-producing cells, are the major coordinators of antiviral immunity; however, their NLRP3-dependent IL-1 beta secretory pathway is poorly studied. Our aim was to determine the functional activity of the IL-1 beta pathway and its possible interaction with the type I IFN pathway in pDCs. We found that potent nuclear factor-kappa B (NF-kappa B) inducers promote higher levels of pro-IL-1 beta during priming compared to those activation signals, which mainly trigger interferon regulatory factor (IRF)-mediated type I IFN production. The generation of cleaved IL-1 beta requires certain secondary signals in pDCs and IFN-alpha or type I IFN-inducing viruses inhibit IL-1 beta production of pDCs, presumably by promoting the expression of various NLRP3 pathway inhibitors. In line with that, we detected significantly lower IL-1 beta production in pDCs of psoriasis patients with elevated IFN-alpha levels. Collectively, our results show that the NLRP3-dependent IL-1 beta secretory pathway is inducible in pDCs; however, it may only prevail under inflammatory conditions, in which the type I IFN pathway is not dominant.