School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology, USA.
Sci Rep. 2017 Mar 14;7:41623. doi: 10.1038/srep41623.
The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. Here we show that exosomes from TLR stimulated cells can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function. We are the first to show that exosomes derived from poly(I:C) stimulated cells induce in vivo macrophage M1-like polarization within murine lymph nodes. These poly(I:C) exosomes demonstrate enhanced trafficking to the node and preferentially recruit neutrophils as compared to control exosomes. This work definitively establishes the differential effector function for exosomes in communicating the TLR activation state of the cell of origin.
先天免疫系统对于快速应对病原体至关重要，而 Toll 样受体（TLR）是这种反应的关键组成部分。纳米囊泡外泌体在免疫中发挥作用，但迄今为止，它们对 TLR 反应传播的确切贡献尚不清楚。在这里，我们展示了来自 TLR 刺激细胞的外泌体可以在体外很大程度上再现 TLR 在远端细胞中的激活。我们可以通过紫外线照射来废除外泌体的远距离信号传递，这表明 RNA 对于它们的效应功能至关重要。我们是第一个证明源自 poly(I:C)刺激细胞的外泌体在体内诱导小鼠淋巴结中巨噬细胞 M1 样极化的人。与对照外泌体相比，这些 poly(I:C)外泌体显示出增强的向淋巴结的转运，并优先招募中性粒细胞。这项工作明确确立了外泌体在传递细胞起源的 TLR 激活状态方面的差异效应功能。
