Human Dendritic Cells Activated via Dectin-1 Are Efficient at Priming Th17, Cytotoxic CD8 T and B Cell Responses
نویسندگان
چکیده
BACKGROUND Dendritic cells capture antigens through PRRs and modulate adaptive immune responses. The type of adaptive immune T cell response generated is dependent upon the type of PRR activated by the microbes. Dectin-1 is a C-type lectin receptor present on dendritic cells. METHODOLOGY/PRINCIPAL FINDINGS Here we show that selective dectin-1 agonist Curdlan can activate human DCs and induce the secretion of large amounts of IL-23, IL-1β, IL-6 and low levels of IL-12p70 as determined by ELISA. The Curdlan-stimulated DCs are efficient at priming naïve CD4 cells to differentiate into Th17 and Th1 cells. Furthermore, these CD4 T cells induce differentiation of B cells to secrete IgG and IgA. In addition, Curdlan-stimulated DCs promote the expansion and differentiation of Granzyme and perforin expressing cytotoxic T lymphocyte that display high cytolytic activity against target tumor cells in vitro. CONCLUSIONS/SIGNIFICANCE These data demonstrate that DCs stimulated through Dectin-1 can generate efficient Th, CTL and B cell responses and can therefore be used as effective mucosal and systemic adjuvants in humans.
منابع مشابه
Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses.
The C-type lectin receptor dectin-1 functions as a pattern recognition receptor for beta-glucans and signals via Syk kinase but independently of the Toll-like receptor (TLR) pathway to regulate expression of innate response genes. Dectin-1 signaling can promote activation of dendritic cells (DCs), rendering them competent to prime Th1 and Th17 responses. Here we show that dectin-1-activated DCs...
متن کاملConcomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8+ T cell responses.
Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4(+) T cell responses. In this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of Ag-specific CD8(+) T cell responses. We fir...
متن کاملDectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells
Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polariz...
متن کاملTLR-4 cooperates with Dectin-1 and mannose receptor to expand Th17 and Tc17 cells induced by Paracoccidioides brasiliensis stimulated dendritic cells
The concomitant use of diverse pattern recognition receptors (PRRs) by innate immune cells can result in synergistic or inhibitory activities that profoundly influence anti-microbial immunity. Dectin-1 and the mannose receptor (MR) are C-type lectin receptors (CLRs) previously reported to cooperate with toll-like receptors (TLRs) signaling in the initial inflammatory response and in the inducti...
متن کاملمروری بر نقش زیرگروههای لنفوسیتهای T در پاتوژنز بیماری مولتیپل اسکلروزیس
Background and Objectives: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of the central nervous system (CNS). Although, the contribution of various cells such as B cells, CD8+ T cells, microglia/macrophages, dendritic cells, asterocytes and mast cells in the pathogenesis of MS have been demonstrated, however, it seems that autoreactive myelin specific CD4+ T cells pla...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 5 شماره
صفحات -
تاریخ انتشار 2010