Journal
CELLULAR IMMUNOLOGY
Volume 289, Issue 1-2, Pages 119-127Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2014.03.016
Keywords
Dendritic cells; NK cells; Exosomes; TLR ligands; Transmembrane TNF; Th1 response
Categories
Funding
- National Institute of Health [I-PO DE13059, RO1 DE14775, RO1 DE17150]
- University of Pittsburgh Cancer Institute
- NIH [P30CA047904]
- Henry L. Hillman Foundation
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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 IFN gamma. 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. Published by Elsevier Inc.
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