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

Abstract

Toll-like receptor 5 (TLR5) agonist flagellin is an effective mucosal adjuvant via intranasal (i.n.) administration. Previous studies demonstrated that the mucosal adjuvanticity of flagellin depends on TLR5 signaling of airway epithelial cells. Since dendritic cells (DCs) play a central role in antigen sensitization and the initiation of primary immune responses, we wondered how DCs were modulated by the intranasally administrated flagellin. In this study, a mouse model of i.n. immunization with ovalbumin (OVA), 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 DCs was associated with TLR5 signaling. In contrary, migration of antigen-loaded DCs from the nasal cavity to the cervical lymph nodes (CLN) and activation of DC in the CLN were both enhanced through TLR5 signaling. Furthermore, for the DCs, flagellin enhanced the expression of CCR7, which was pivotal for DCs in the priming site migrating to draining lymph nodes. Interestingly, the migration, activation and chemokine receptor expression levels of antigen-loaded DC were all significantly higher than that of bystander DCs. In conclusion, intranasally administrated flagellin enhanced TLR5-dependent antigen loaded DCs’ migration and activation, but not antigen uptake.

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

“…1h ), despite 3R-NC + KFDi.n contained lower amount of both parts of the target antigen and the adjuvant. Similar to our previous reports, 24 , 29 upon uptake by DCs in the nasal region, the antigen-loaded DCs would become activated and migrate to the CLN (Supplementary Fig. 3a ).…”

“…Toll-like receptor 5 (TLR5) agonist, the recombinant flagellin, has been intensively investigated and optimized as a safe and effective mucosal adjuvant in animal model. 23 , 24 In developing mucosal vaccines for dental caries, 25 we observed that the flagellin adjuvanted subunit mucosal vaccines can elicit enduring antibodies, lasting up to 13 months in mice (Supplementary Fig. 1 ).…”

Tolerogenic dendritic cells in radiation-induced lung injury

“…Notably, it has been reported that many conventional DCs(cDCs) are located in the mucous membranes of the airway ducts ( 107 – 109 ). These cells extend pseudopods between epithelial cells to capture antigens present within the airway cavity ( 102 , 110 , 111 ). Based on their functional differences, cDCs are further categorized into two subsets: cDC1 and cDC2.…”