Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; and.
Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; and
J Immunol. 2021 Apr 1;206(7):1419-1423. doi: 10.4049/jimmunol.2001373. Epub 2021 Mar 8.
Invasive fungal infections have become a leading cause of death among immunocompromised patients, leading to around 1.5 million deaths per year globally. The molecular mechanisms by which hosts defend themselves against fungal infection remain largely unclear, which impedes the development of antifungal drugs and other treatment options. In this article, we show that the tyrosine kinase receptor EPH receptor B2 (EPHB2), together with dectin-1, recognizes β-glucan and activates downstream signaling pathways. Mechanistically, we found that EPHB2 is a kinase for Syk and is required for Syk phosphorylation and activation after dectin-1 ligand stimulation, whereas dectin-1 is critical for the recruitment of Syk. -deficient mice are susceptible to -induced fungemia model, which also supports the role of EPHB2 in antifungal immunity. Overall, we provide evidence that EPHB2 is a coreceptor for the recognition of dectin-1 ligands and plays an essential role in antifungal immunity by phosphorylating Syk.
侵袭性真菌感染已成为免疫功能低下患者死亡的主要原因，全球每年导致约 150 万人死亡。宿主抵御真菌感染的分子机制在很大程度上仍不清楚，这阻碍了抗真菌药物和其他治疗方法的发展。在本文中，我们表明酪氨酸激酶受体 Eph 受体 B2 (EPHB2) 与 dectin-1 一起识别β-葡聚糖并激活下游信号通路。在机制上，我们发现 EPHB2 是 Syk 的激酶，并且在 dectin-1 配体刺激后 Syk 磷酸化和激活所必需的，而 dectin-1 对于 Syk 的募集至关重要。Ephb2 缺陷小鼠易患念珠菌诱导的菌血症模型，这也支持了 Ephb2 在抗真菌免疫中的作用。总的来说，我们提供的证据表明 Ephb2 是 dectin-1 配体识别的核心受体，通过磷酸化 Syk 发挥在抗真菌免疫中的重要作用。
