Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
Department of Pathology, Duke University, Durham, NC 27710, USA.
Sci Adv. 2019 Jan 2;5(1):eaav0216. doi: 10.1126/sciadv.aav0216. eCollection 2019 Jan.
Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, a peptide MC activator (MCA), enhances clearance of from infected mouse skins and accelerates healing of dermonecrotic lesions. Mastoparan functions by activating connective tissue MCs (CTMCs) via the MRGPRX2 (Mas-related G protein-coupled receptor member X2) receptor. Peripheral CTMC activation, in turn, enhances recruitment of bacteria-clearing neutrophils and wound-healing CD301b dendritic cells. Consistent with MCs playing a master coordinating role, MC activation also augmented migration of various antigen-presenting dendritic cells to draining lymph nodes, leading to stronger protection against a second infection challenge. MCAs therefore orchestrate both the innate and adaptive immune arms, which could potentially be applied to combat peripheral infections by a broad range of pathogens.
肥大细胞 (MCs) 战略性地分布在屏障部位，并预先储存各种免疫细胞募集细胞因子，使它们成为选择性激活以治疗外周感染的理想靶点。在这里，我们报告说，用肥大细胞激活肽 (MCA) 蜂毒素局部治疗可增强受感染小鼠皮肤中 的清除，并加速皮肤坏死病变的愈合。蜂毒素通过激活连接组织 MCs (CTMCs) 发挥作用，通过 MRGPRX2（Mas 相关 G 蛋白偶联受体成员 X2）受体。反过来，外周 CTMC 的激活增强了清除细菌的中性粒细胞和伤口愈合的 CD301b 树突状细胞的募集。与 MC 发挥主导协调作用一致，MC 激活还增强了各种抗原呈递树突状细胞向引流淋巴结的迁移，从而对第二次感染挑战产生更强的保护作用。因此，MCAs 协调先天和适应性免疫，这可能适用于对抗广泛的病原体引起的外周感染。
