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

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

Author information

1
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
2
Rush University Medical Center, Department of Neurosurgery, Chicago, IL, USA.
3
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Pathology, Pittsburgh, PA, USA; Department of Immunology, Pittsburgh, PA, USA. Electronic address: vujanovicnl@msx.upmc.edu.

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

PMID:
24759079
PMCID:
PMC4045011
DOI:
10.1016/j.cellimm.2014.03.016
[Indexed for MEDLINE]
Free PMC Article

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