Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells

Cell Immunol. May-Jun 2014;289(1-2):119-27. doi: 10.1016/j.cellimm.2014.03.016. Epub 2014 Apr 8.

Abstract

Dendritic cells (DCs) are the major sentinel, antigen-presenting and regulatory components of the immune system. One of the central DC functions is to rapidly sense and alert host immune system of a pathogen invasion. In the present study, we investigated the role of DC exosomes (DCex) in this sentinel function. We demonstrated that DCex could bind bacterial Toll-like-receptor ligands (TLR-Ls), and acquire their ability to strongly activate bystander DCs. Consequently, bystander DCs enhance the expression of transmembrane tumor necrosis factor, secretion of proinflammatory cytokines and cross-talk with natural killer cells leading to the elevated secretion of IFNγ. These findings newly show that DCex can bind and cross-present TLR-Ls to innate-immunity effector cells, and indicate a potent mechanism to systemically alert the host immune system of pathogen invasion. They also suggest a potential novel strategy to generate effective vaccines by binding TLR-L-immune adjuvants to DCex.

Keywords: Dendritic cells; Exosomes; NK cells; TLR ligands; Th1 response; Transmembrane TNF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Bacterial Outer Membrane Proteins / immunology*
  • Bystander Effect / immunology*
  • Dendritic Cells / immunology*
  • Exosomes / immunology*
  • Female
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Lipopeptides / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Toll-Like Receptor 1 / agonists
  • Toll-Like Receptor 2 / agonists
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Bacterial Outer Membrane Proteins
  • Lipopeptides
  • Pam(3)CSK(4) peptide
  • TLR protein, bacteria
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma