Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Dent Res. 2020 Jul;99(8):882-890. doi: 10.1177/0022034520919107. Epub 2020 May 11.
Mast cells are multifunctional immune cells that are found most abundantly at host-environment interfaces, such as the skin, respiratory tract, and oral/gastrointestinal mucosa. Not surprisingly, mast cells act as sentinel cells that sense microbial attacks and initiate a protective immune response and promote healing. Although mast cells share many features with other innate immune effector cells, such as neutrophils and macrophages, they uniquely interact closely with blood vessels and release an extensive set of mediators for the recruitment of innate and adaptive immune cells. A novel human G protein-coupled receptor (GPCR), known as Mas-related GPCR-X2 (MRGPRX2, mouse ortholog, MrgprB2), has recently been identified, which is expressed on mast cells but not neutrophils and macrophages. Interestingly, activation of MrgprB2 by bacteria-derived quorum-sensing peptides inhibits bacterial growth, prevents biofilm formation, and leads to the recruitment of neutrophils to effectively clear bacteria. Furthermore, host defense antimicrobial peptides and small-molecule peptide mimetics also activate mast cells via MRGPRX2/B2. MrgprB2-mediated activation of local mast cells also clears cutaneous bacterial infection, promotes healing, and protects against reinfection. In addition to their role in host defense, mast cells contribute to a number of chronic inflammatory diseases such as periodontitis, neurogenic inflammation, and inflammatory pain likely via the activation of MRGPRX2. In this review, we discuss the roles of MRGPRX2/B2 in the clearance of bacterial infection, wound healing, periodontal disease, neurogenic inflammation, and inflammatory pain. We propose that harnessing mast cells' host defense and immunomodulatory properties via the activation of MRGPRX2 may lead to novel approaches for the treatment of drug-resistant bacterial infections. On the other hand, increased MRGPRX2 expression on mast cells and their inappropriate activation may contribute to periodontitis, neurogenic inflammation, and inflammatory pain. Thus, targeting MRGPRX2 could provide novel approaches to modulate these conditions.
肥大细胞是多功能免疫细胞，在宿主-环境界面（如皮肤、呼吸道和口腔/胃肠道黏膜）中最为丰富。毫不奇怪，肥大细胞充当感应微生物攻击并启动保护性免疫反应和促进愈合的哨兵细胞。尽管肥大细胞与其他先天免疫效应细胞（如中性粒细胞和巨噬细胞）具有许多共同特征，但它们与血管密切相互作用，并释放广泛的介质，用于招募先天和适应性免疫细胞。最近发现了一种新型人类 G 蛋白偶联受体（GPCR），称为与 Mas 相关的 GPCR-X2（MRGPRX2，小鼠同源物，MrgprB2），它表达在肥大细胞上，但不表达在中性粒细胞和巨噬细胞上。有趣的是，细菌衍生的群体感应肽激活 MrgprB2 可抑制细菌生长、防止生物膜形成，并导致中性粒细胞募集以有效清除细菌。此外，宿主防御性抗菌肽和小分子肽模拟物也通过 MRGPRX2/B2 激活肥大细胞。MrgprB2 介导的局部肥大细胞激活还可清除皮肤细菌感染、促进愈合并防止再感染。除了在宿主防御中的作用外，肥大细胞还通过激活 MRGPRX2 参与许多慢性炎症性疾病，如牙周炎、神经源性炎症和炎性疼痛。在这篇综述中，我们讨论了 MRGPRX2/B2 在清除细菌感染、伤口愈合、牙周病、神经源性炎症和炎性疼痛中的作用。我们提出，通过激活 MRGPRX2 利用肥大细胞的宿主防御和免疫调节特性可能会为治疗耐药性细菌感染开辟新途径。另一方面，肥大细胞上 MRGPRX2 的表达增加及其不当激活可能导致牙周炎、神经源性炎症和炎性疼痛。因此，靶向 MRGPRX2 可能为调节这些疾病提供新的方法。
