The Syk–NFAT–IL-2 Pathway in Dendritic Cells Is Required for Optimal Sterile Immunity Elicited by Alum Adjuvants

摘要: Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators immune responses, but little is known about pathways used by DCs to sense alum and, in turn, activate T B cells. In this article, we show that adjuvanticity requires IL-2 specifically released DCs, even when cell secretion intact. We demonstrate alum, well other sterile particulates, such uric acid crystals, induces produce following initiation actin-mediated phagocytosis leads Src Syk kinase activation, Ca2+ mobilization, calcineurin-dependent activation NFAT, master transcription factor regulating expression. Using chimeric mice, DC-derived required for maximal proliferation CD4+ optimal humoral responses alum-adjuvanted immunization. These data identify key mediator vivo Src-Syk pathway potential leverage point rational design novel adjuvants.