Immobile ligands enhance FcγR-TLR2/1 crosstalk by promoting interface overlap of receptor clusters.
Immobile ligands enhance FcγR-TLR2/1 crosstalk by promoting interface overlap of receptor clusters.
复制标题
固定配体通过促进受体簇的界面重叠来增强FcγR-TLR2/1 串扰。
DOI：
10.1016/j.bpj.2022.02.010
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发表时间：
2022
影响因子：
3.4
通讯作者：
Yu,Yan
中科院分区：
文献类型：
--
作者：
Li,Miao;Lee,Seonik;Zahedian,Maryam;Ding,Chuanlin;Yan,Jun;Yu,Yan
先天免疫细胞通过同时刺激多个受体来检测病原体，但细胞如何利用受体串扰来引发适合环境的反应尚不清楚。在这里，我们揭示了 FcγR-TLR2/1 串扰引起的巨噬细胞的炎症反应与模型病原体膜内的配体迁移率成反比。其机制是 FcγR 和 TLR2/1 形成单独的纳米团簇，在串扰过程中在其界面处相互作用。移动性较低的配体会诱导受体纳米簇之间更强的相互作用和更多重叠，从而增强信号传导。与免疫受体共定位以协同其信号传导的普遍观点不同，我们的结果表明 FcγR-TLR2/1 串扰是通过非共定位受体纳米团簇之间的界面相互作用发生的，而非共定位受体纳米团簇受配体迁移率调节。这表明先天免疫细胞可以利用配体的物理特性来微调宿主反应的机制。
Innate immune cells detect pathogens through simultaneous stimulation of multiple receptors, but how cells use the receptor crosstalk to elicit context-appropriate responses is unclear. Here, we reveal that the inflammatory response of macrophages from FcγR-TLR2/1 crosstalk inversely depends on the ligand mobility within a model pathogen membrane. The mechanism is that FcγR and TLR2/1 form separate nanoclusters that interact at their interfaces during crosstalk. Less mobile ligands induce stronger interactions and more overlap between the receptor nanoclusters, leading to enhanced signaling. Different from the prevailing view that immune receptors colocalize to synergize their signaling, our results show that FcγR-TLR2/1 crosstalk occurs through interface interactions between non-colocalizing receptor nanoclusters, which are modulated by ligand mobility. This suggests a mechanism by which innate immune cells could use physical properties of ligands to fine-tune host responses.