Enhanced TLR5-dependent migration and activation of antigen-loaded airway dendritic cells by flagellin
Enhanced TLR5-dependent migration and activation of antigen-loaded airway dendritic cells by flagellin
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DOI：
10.1093/jleuko/qiad030
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发表时间：
2023-04-24
影响因子：
5.5
通讯作者：
Zhong，Maohua
中科院分区：
文献类型：
--
作者：
Li，Xu;Cao，Yuan;Zhong，Maohua
TLR5激动剂鞭毛蛋白是通过鼻内给药的有效粘膜佐剂。以往的研究表明鞭毛蛋白的粘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应答的启动中起核心作用，我们想知道鼻内施用的鞭毛蛋白如何调节树突状细胞。在本研究中，使用了在存在或不存在鞭毛蛋白的情况下用卵清蛋白（一种模型抗原）鼻内免疫的小鼠模型。我们发现，鼻内给药鞭毛蛋白增强共同管理的抗原特异性抗体反应和T细胞克隆扩增TLR5依赖的方式。然而，无论是进入鼻固有层的鞭毛蛋白，也没有共同管理的抗原鼻常驻树突状细胞的摄取与TLR5信号。相反，负载抗原的树突状细胞从鼻腔向颈部淋巴结的迁移和颈部淋巴结中树突状细胞的活化均通过TLR5信号传导增强。此外，对于树突状细胞，鞭毛蛋白增强CCR7的表达，这是树突状细胞在引发部位迁移到引流淋巴结的关键。有趣的是，负载抗原的树突状细胞的迁移、活化和趋化因子受体表达水平均显著高于旁观者树突状细胞。总之，鼻内给予鞭毛蛋白增强TLR5依赖性抗原负载树突状细胞的迁移和活化，但不增强抗原摄取。
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.