Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk.
Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk.
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DOI：
10.1038/s41598-021-92910-9
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发表时间：
2021-06-28
影响因子：
4.6
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Li W;Li M;Anthony SM;Yu Y
许多先天性免疫受体协同作用以检测和引发对病原体的免疫应答，但是控制受体之间的相互作用和信号传导串扰的物理机制尚不清楚。在这项研究中，我们报告了Fc γ受体（FcγR）和Toll样受体（TLR）2/1之间的信号串扰可以是整体协同或抑制，这取决于吞噬体膜上受体对之间的空间接近度。使用几何操作策略，我们物理地改变了FcγR和TLR 2在单个吞噬体上的空间分布。我们证明FcγR和TLR 2/1之间的信号协同作用取决于受体的接近程度，并随着它们之间空间间隔的增加而减少。然而，FcγRIIb对TLR 2依赖性信号传导的抑制作用始终存在，并且与受体邻近无关。整个细胞反应是这两种机制的综合。这项研究提供了定量证据，表明FcγR和TLR 2之间的纳米级接近是其信号串扰的关键调节机制。
Many innate immune receptors function collaboratively to detect and elicit immune responses to pathogens, but the physical mechanisms that govern the interaction and signaling crosstalk between the receptors are unclear. In this study, we report that the signaling crosstalk between Fc gamma receptor (FcγR) and Toll-like receptor (TLR)2/1 can be overall synergistic or inhibitory depending on the spatial proximity between the receptor pair on phagosome membranes. Using a geometric manipulation strategy, we physically altered the spatial distribution of FcγR and TLR2 on single phagosomes. We demonstrate that the signaling synergy between FcγR and TLR2/1 depends on the proximity of the receptors and decreases as spatial separation between them increases. However, the inhibitory effect from FcγRIIb on TLR2-dependent signaling is always present and independent of receptor proximity. The overall cell responses are an integration from these two mechanisms. This study presents quantitative evidence that the nanoscale proximity between FcγR and TLR2 functions as a key regulatory mechanism in their signaling crosstalk.
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