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

PLoS One. 2010 Oct 18;5(10):e13418. doi: 10.1371/journal.pone.0013418.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / metabolism
  • Lectins, C-Type
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / physiology*

Substances

  • Immunoglobulin A
  • Immunoglobulin G
  • Lectins, C-Type
  • Lipopolysaccharides
  • Membrane Proteins
  • Nerve Tissue Proteins
  • dectin 1