Human dendritic cells activated via dectin-1 are efficient at priming Th17, cytotoxic CD8 T and B cell responses

• Published in: PloS one Vol. 5; no. 10; p. e13418
• Main Authors: Agrawal, Sudhanshu, Gupta, Sudhir, Agrawal, Anshu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.10.2010; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Adjuvants; Antigens; Arthritis; B cells; Cancer; CD4 antigen; CD8 antigen; Cell Differentiation; Chemotherapy; Cytokines; Cytolytic activity; Cytotoxicity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Differentiation; Enzyme-linked immunosorbent assay; Experiments; Helper cells; Humans; Immune response; Immunoglobulin A; Immunoglobulin A - metabolism; Immunoglobulin G; Immunoglobulin G - metabolism; Immunology; Immunology/Immune Response; Immunology/Immunomodulation; Immunology/Innate Immunity; Interleukin 12; Interleukin 23; Interleukin 6; Lectins; Lectins, C-Type; Ligands; Lipopolysaccharides - pharmacology; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Membrane Proteins - physiology; Mucosa; Mycobacterium tuberculosis; Nerve Tissue Proteins - physiology; Pattern recognition; Perforin; Priming; Psoriasis; Rodents; Studies; T cell receptors; T cells; Tuberculosis; Tumor cells; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013418

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. 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. 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.