Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells.
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.
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Andrea
A
Sobo-Vujanovic
Rush University Medical Center, Department of Neurosurgery, Chicago, IL, USA.
Stephan
S
Munich
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.
Nikola L
NL
Vujanovic
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D024201:Bystander Effect / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D055354:Exosomes / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D055666:Lipopeptides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D051194:Toll-Like Receptor 1 / Q000819:agonists; D051195:Toll-Like Receptor 2 / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; C419843:TLR protein, bacteria; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
Dendritic cells; Exosomes; NK cells; TLR ligands; Th1 response; Transmembrane TNF