Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, #2 Huangjiahu West Road, Hongshan District, Wuhan, Hubei 430065, China.
Analytical & Testing Center, Wuhan University of Science and Technology, #2 Huangjiahu West Road, Hongshan District, Wuhan, Hubei 430065, China.
J Leukoc Biol. 2023 Jun 1;113(6):567-576. doi: 10.1093/jleuko/qiad030.
TLR5 agonist flagellin is an effective mucosal adjuvant via intranasal administration. Previous studies demonstrated that the mucosal adjuvanticity of flagellin depends on TLR5 signaling of airway epithelial cells. Since dendritic cells play a central role in antigen sensitization and the initiation of primary immune responses, we wondered how dendritic cells were modulated by the intranasally administrated flagellin. In this study, a mouse model of intranasal immunization with ovalbumin, a model antigen, in the presence or absence of flagellin was utilized. We found that nasal administration of flagellin enhanced the coadministered antigen-specific antibody responses and T-cell clonal expansion in a TLR5-dependent manner. However, neither the entering of flagellin to nasal lamina propria nor the uptake of coadministered antigen by nasal resident dendritic cells was associated with TLR5 signaling. In contrast, migration of antigen-loaded dendritic cells from the nasal cavity to the cervical lymph nodes and activation of dendritic cells in the cervical lymph nodes were both enhanced through TLR5 signaling. Furthermore, for the dendritic cells, flagellin enhanced the expression of CCR7, which was pivotal for dendritic cells in the priming site migrating to draining lymph nodes. Interestingly, the migration, activation, and chemokine receptor expression levels of antigen-loaded dendritic cells were all significantly higher than that of bystander dendritic cells. In conclusion, intranasally administrated flagellin enhanced TLR5-dependent antigen-loaded dendritic cells' migration and activation but not antigen uptake.
TLR5 激动剂鞭毛蛋白通过鼻腔给药是一种有效的黏膜佐剂。先前的研究表明，鞭毛蛋白的黏膜佐剂活性依赖于气道上皮细胞的 TLR5 信号。由于树突状细胞在抗原致敏和初级免疫反应的启动中发挥核心作用，我们想知道鼻内给予的鞭毛蛋白如何调节树突状细胞。在这项研究中，利用卵清蛋白（一种模型抗原）鼻内免疫的小鼠模型，研究了鞭毛蛋白的存在与否。结果发现，鞭毛蛋白的鼻腔给药以 TLR5 依赖性方式增强了共给予的抗原特异性抗体反应和 T 细胞克隆扩增。然而，鞭毛蛋白进入鼻固有层或鼻腔常驻树突状细胞摄取共给予的抗原都与 TLR5 信号无关。相反，通过 TLR5 信号增强了负载抗原的树突状细胞从鼻腔向颈淋巴结的迁移以及颈淋巴结中树突状细胞的激活。此外，对于树突状细胞，鞭毛蛋白增强了 CCR7 的表达，这对于在启动部位迁移到引流淋巴结的树突状细胞至关重要。有趣的是，负载抗原的树突状细胞的迁移、激活和趋化因子受体表达水平均明显高于旁观者树突状细胞。总之，鼻内给予的鞭毛蛋白增强了 TLR5 依赖性负载抗原的树突状细胞的迁移和激活，但不增强抗原摄取。
