Inflammation is a pathophysiological response of innate immunity to infection or tissue damage. This response is among others triggered by factors released by damaged or dying cells, termed damage-associated molecular pattern (DAMP) molecules that act as danger signals. DAMPs interact with pattern recognition receptors (PRRs) to contribute to the induction of inflammation. However, how released peroxiredoxins (PRDXs) are able to activate PRRs, such as Toll-like receptors (TLRs), remains elusive. Here, we used force-distance curve-based atomic force microscopy to investigate the molecular mechanisms by which extracellular human PRDX5 can activate a proinflammatory response. Single-molecule experiments demonstrated that PRDX5 binds to purified TLR4 receptors, on macrophage-differentiated THP-1 cells, and on human TLR4-transfected CHO cells. These findings suggest that extracellular PRDX5 can specifically trigger a proinflammatory response. Moreover, our work also revealed that PRDX5 binding induces a cellular mechanoresponse. Collectively, this study provides insights into the role of extracellular PRDX5 in innate immunity.

中文翻译：

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原子力显微镜在Peroxiredoxin-5和TLR4之间的活细胞上测量的特定相互作用：与先天免疫机制的相关性。

炎症是先天免疫对感染或组织损伤的病理生理反应。这种反应是由受损或濒临死亡的细胞释放的因素触发的，这些因素称为损害相关分子模式（DAMP）分子，可作为危险信号。DAMP与模式识别受体（PRR）相互作用，有助于诱发炎症。但是，释放的过氧化物酶（PRDXs）如何激活PRR，例如Toll样受体（TLRs），仍然遥遥无期。在这里，我们使用基于力-距离曲线的原子力显微镜研究了细胞外人类PRDX5可以激活促炎反应的分子机制。单分子实验表明，PRDX5在巨噬细胞分化的THP-1细胞和人TLR4转染的CHO细胞上与纯化的TLR4受体结合。这些发现表明细胞外PRDX5可以特异性触发促炎反应。此外，我们的工作还揭示了PRDX5结合可诱导细胞机械反应。总的来说，这项研究提供了关于细胞外PRDX5在先天免疫中的作用的见解。