Macrophage activation on "phagocytic synapse" arrays: Spacing of nanoclustered ligands directs TLR1/2 signaling with an intrinsic limit.
Macrophage activation on "phagocytic synapse" arrays: Spacing of nanoclustered ligands directs TLR1/2 signaling with an intrinsic limit.
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DOI：
10.1126/sciadv.abc8482
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发表时间：
2020-12
期刊：
影响因子：
13.6
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Li M;Wang H;Li W;Xu XG;Yu Y
TLR1/2的聚集是将配体的空间线索整合到细胞水平激活事件中的驱动因素。微生物组分激活toll样受体异二聚体1/2 （TLR1/2）在宿主对病原体的免疫应答中起关键作用。TLR1/2信号对配体的化学结构很敏感，但其对微生物表面配体空间分布的依赖性尚不清楚。在这里，我们通过设计一个人工的“吞噬突触”纳米阵列平台来模拟细胞-微生物界面，揭示了tlr1 /2触发的免疫反应与配体簇间距之间的定量关系。配体间距决定了受体簇在细胞表面的接近程度，从而决定了巨噬细胞的促炎反应。然而，当受体纳米簇彼此相邻时，细胞反应在小配体间隔处达到最大。我们的研究证明了利用空间模式配体调节先天免疫的可行性。这表明TLR1/2受体簇在将配体的空间线索整合到细胞水平的激活事件中起驱动作用。
The clustering of TLR1/2 acts as a driver in integrating the spatial cues of ligands into cell-level activation events. The activation of Toll-like receptor heterodimer 1/2 (TLR1/2) by microbial components plays a critical role in host immune responses against pathogens. TLR1/2 signaling is sensitive to the chemical structure of ligands, but its dependence on the spatial distribution of ligands on microbial surfaces remains unexplored. Here, we reveal the quantitative relationship between TLR1/2-triggered immune responses and the spacing of ligand clusters by designing an artificial “phagocytic synapse” nanoarray platform to mimic the cell-microbe interface. The ligand spacing dictates the proximity of receptor clusters on the cell surface and consequently the pro-inflammatory responses of macrophages. However, cell responses reach their maximum at small ligand spacings when the receptor nanoclusters become adjacent to one another. Our study demonstrates the feasibility of using spatially patterned ligands to modulate innate immunity. It shows that the receptor clusters of TLR1/2 act as a driver in integrating the spatial cues of ligands into cell-level activation events.
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