Airway structural cells regulate TLR5-mediated mucosal adjuvant activity

Authors
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.
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
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.
Fil: Van Maele, Laurye. Institut Pasteur de Lille. Lille; Francia. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Fougeron, Delphine. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia
Fil: Janot, Laurent. University of Orléans. Orléans; Francia. Institut de Transgenose. Orleans; Francia
Fil: Didierlaurent, A.. Imperial College of London. Londres; Reino Unido
Fil: Cayet, D.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia
Fil: Tabareau, J.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia
Fil: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Corvo Chamaillard, S.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia
Fil: Boulenoir, S.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia
Fil: Jeffs, S. Imperial College of London. Londres; Reino Unido
Fil: Vande Walle, L. Department of Medical Protein Research. Ghent; Bélgica. University of Ghent; Bélgica
Fil: Lamkanfi, M.. Department of Medical Protein Research. Ghent; Bélgica. University of Ghent; Bélgica
Fil: Lemoine, Y.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Francia
Fil: Erard, F.. Institut de Transgenose. Orleans; Francia. University of Orléans. Orléans; Francia
Fil: Hot, D.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Francia
Fil: Hussell, Tracy. Imperial College of London. Londres; Reino Unido. University of Manchester; Reino Unido
Fil: Ryffel, B.. Institut de Transgenose. Orleans; Francia. University of Orléans. Orléans; Francia
Fil: Benecke, Arndt G.. Institut des Hautes Études Scientifiques and Centre National de la Recherche Scientifique; Francia
Fil: Sirard, J.C.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Francia
Subject
Adaptive immunity
Antigen-presenting cells
Mucosal immunology
Toll-like receptors
Inmunología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/32310