University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Rush University Medical Center, Department of Neurosurgery, Chicago, IL, USA.
Cell Immunol. 2014 May-Jun;289(1-2):119-27. doi: 10.1016/j.cellimm.2014.03.016. Epub 2014 Apr 8.
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.
树突状细胞 (DCs) 是免疫系统中主要的哨兵、抗原呈递和调节成分。DC 的主要功能之一是快速感知和提醒宿主免疫系统病原体的入侵。在本研究中，我们研究了 DC 外泌体 (DCex) 在这种哨兵功能中的作用。我们证明 DCex 可以结合细菌 Toll 样受体配体 (TLR-Ls)，并获得强烈激活旁观者 DCs 的能力。因此，旁观者 DCs 增强跨膜肿瘤坏死因子的表达、促炎细胞因子的分泌和与自然杀伤细胞的串扰，导致 IFNγ 的分泌增加。这些发现新表明，DCex 可以结合并交叉呈递 TLR-Ls 给先天免疫效应细胞，并表明一种有效的机制可以系统地提醒宿主免疫系统病原体的入侵。它们还为通过将 TLR-L-免疫佐剂结合到 DCex 上来产生有效疫苗提供了一种潜在的新策略。
