Enhanced TLR5-dependent migration and activation of antigen-loaded airway dendritic cells by flagellin

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.

Keywords: cell activation; cell migration; dendritic cells; flagellin; mucosal adjuvant.