Alarmin human a defensin HNP1 activates plasmacytoid dendritic cells by triggering NF-κB and IRF1 signaling pathways

Human neutrophil peptide 1 (HNP1), a predominant alpha defensin in the azurophilic granules of human neutrophils, is an alarmin capable of inducing the migration and maturation of human myeloid/conventional dendritic cells. However, it is not determined whether it can activate plasmacytoid dendritic cells (pDCs). Herein, we found that both human pDCs and CAL-1 cells, a pDC-like cell line, produced IFN alpha upon treatment with HNP1. Additionally, HNP1 could promote CpG ODN-induced pDC production of proinflammatory cytokines including IFN alpha. HNP1 triggered activation of NF-kappa B and nuclear translocation of interferon regulatory factor 1 (IRFI) in CAL-1 cells. HNP1 upregulation of cytokine expression in pDCs was inhibited by blockade of NF-kappa B activation or knockdown of IRF1, demonstrating the importance of these two signaling events in HNP1-induced pDC activation. Using a human pDC-nude mouse model, HNP1 was shown to induce IFN alpha, production by human pDCs in vivo. Thus, HNP1 can activate human pDCs using NF-kappa B and IRF signaling pathways, and HNP-induced IFN production may participate in the inflammatory pathogenesis in certain authoimmune diseases such as rheumatoid arthritis. (C) 2016 Elsevier Ltd. All rights reserved.