Airway structural cells regulate TLR5-mediated mucosal adjuvant activity

Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic...

ver descrição completa

Detalhes bibliográficos
Autores: Van Maele, Laurye, Fougeron, Delphine, Janot, Laurent, Didierlaurent, A., Cayet, D., Tabareau, J., Rumbo, Martín, Corvo Chamaillard, S., Boulenoir, S., Jeffs, S, Vande Walle, L, Lamkanfi, M., Lemoine, Y., Erard, F., Hot, D., Hussell, Tracy, Ryffel, B., Benecke, Arndt G., Sirard, J.C.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/32310
Acesso em linha:http://hdl.handle.net/11336/32310
Access Level:acceso abierto
Palavra-chave:Adaptive Immunity
Antigen-Presenting Cells
Mucosal Immunology
Toll-Like Receptors
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic cells contributes to flagellin’s mucosal adjuvant activity. Nasal administration of flagellin enhanced T-cell-mediated immunity, and systemic and secretory antibody responses to coadministered antigens in a TLR5-dependent manner. Mucosal adjuvant activity was not affected by either abrogation of TLR5 signaling in hematopoietic cells or the presence of flagellin-specific, circulating neutralizing antibodies. We found that flagellin is rapidly degraded in conducting airways, does not translocate into lung parenchyma and stimulates an early immune response, suggesting that TLR5 signaling is regionalized. The flagellin-specific early response of lung was regulated by radioresistant cells expressing TLR5 (particularly the airway epithelial cells). Flagellin stimulated the epithelial production of a small set of mediators that included the chemokine CCL20, which is known to promote APC recruitment in mucosal tissues. Our data suggest that (i) the adjuvant activity of TLR agonists in mucosal vaccination may require TLR stimulation of structural cells and (ii) harnessing the effect of adjuvants on epithelial cells can improve mucosal vaccines.

Registos relacionados