美国哈佛医学院Isaac M. Chiu研究小组发现，金黄色葡萄球菌通过V8蛋白酶-PAR1轴驱动瘙痒和划痕诱发的皮肤损伤。相关论文于2023年11月22日在线发表于《细胞》期刊。
研究人员发现与皮肤瘙痒症有关的细菌病原体金黄色葡萄球菌（S. aureus）能直接激活瘙痒感受神经元，从而引起瘙痒。皮肤暴露于S. aureus会引起剧烈瘙痒和划痕诱发的损伤。通过测试多种同源细菌突变体的毒力因子，研究人员发现S. aureus丝氨酸蛋白酶V8是唤起自发性瘙痒和异体瘙痒的关键介质。V8能切割小鼠和人类感觉神经元上的蛋白酶激活受体1（PAR1）。通过基因缺陷、小干扰RNA（siRNA）敲除或药物阻断等方法靶向PAR1，可减少V8和S. aureus暴露引起的瘙痒和皮肤损伤。因此，研究人员确定了一种致痒细菌因子的作用机制，并证明了抑制V8-PAR1信号转导治疗瘙痒的潜力。
据了解，痒是一种令人不快的感觉，会唤起抓挠的欲望。皮肤屏障经常接触微生物及其产物。然而，微生物在瘙痒产生中的作用尚不清楚。
附：英文原文
Title: S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis
Author: Liwen Deng, Flavia Costa, Kimbria J. Blake, Samantha Choi, Arundhasa Chandrabalan, Muhammad Saad Yousuf, Stephanie Shiers, Daniel Dubreuil, Daniela Vega-Mendoza, Corinne Rolland, Celine Deraison, Tiphaine Voisin, Michelle D. Bagood, Lucia Wesemann, Abigail M Frey, Joseph S. Palumbo, Brian J. Wainger, Richard L. Gallo, Juan-Manuel Leyva-Castillo, Nathalie Vergnolle, Theodore J. Price, Rithwik Ramachandran, Alexander R. Horswill, Isaac M. Chiu
Issue&Volume: 2023/11/22
Abstract: Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrieris constantly exposed to microbes and their products. However, the role of microbesin itch generation is unknown. Here, we show that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptorsensory neurons to drive itch. Epicutaneous S. aureus exposure causes robust itch and scratch-induced damage. By testing multiple isogenicbacterial mutants for virulence factors, we identify the S. aureus serine protease V8 as a critical mediator in evoking spontaneous itch and alloknesis.V8 cleaves proteinase-activated receptor 1 (PAR1) on mouse and human sensory neurons.Targeting PAR1 through genetic deficiency, small interfering RNA (siRNA) knockdown,or pharmacological blockade decreases itch and skin damage caused by V8 and S. aureus exposure. Thus, we identify a mechanism of action for a pruritogenic bacterial factorand demonstrate the potential of inhibiting V8-PAR1 signaling to treat itch.
DOI: 10.1016/j.cell.2023.10.019
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01164-9