TLR5型
鞭毛蛋白
树突状细胞
抗原
抗原提呈细胞
生物
免疫学
C-C趋化因子受体7型
细胞生物学
CD40
抗原呈递
免疫系统
Toll样受体
T细胞
细胞毒性T细胞
趋化因子
受体
先天免疫系统
趋化因子受体
体外
生物化学
作者
Xu Li,Yuan Cao,Man Mou,Jianlun Li,Si‐Yao Huang,Ejuan Zhang,Huimin Yan,Jingyi Yang,Ma Zhong
标识
DOI:10.1093/jleuko/qiad030
摘要
Abstract 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.
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