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Airway structural cells regulate TLR5-mediated mucosal adjuvant activity

(2014) MUCOSAL IMMUNOLOGY. 7(3). p.489-500
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Bioinformatics: from nucleotids to networks (N2N)
Abstract
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.
Keywords
DENDRITIC CELLS, TOLL-LIKE RECEPTORS, IN-VIVO, BACTERIAL FLAGELLIN, CELLULAR MECHANISMS, NEGATIVE REGULATOR, LAMINA PROPRIA, INNATE IMMUNITY, ADAPTIVE IMMUNITY, INTESTINAL EPITHELIAL-CELLS

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Citation

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Chicago
Van Maele, L, D Fougeron, L Janot, A Didierlaurent, D Cayet, J Tabareau, M Rumbo, et al. 2014. “Airway Structural Cells Regulate TLR5-mediated Mucosal Adjuvant Activity.” Mucosal Immunology 7 (3): 489–500.
APA
Van Maele, L., Fougeron, D., Janot, L., Didierlaurent, A., Cayet, D., Tabareau, J., Rumbo, M., et al. (2014). Airway structural cells regulate TLR5-mediated mucosal adjuvant activity. MUCOSAL IMMUNOLOGY, 7(3), 489–500.
Vancouver
1.
Van Maele L, Fougeron D, Janot L, Didierlaurent A, Cayet D, Tabareau J, et al. Airway structural cells regulate TLR5-mediated mucosal adjuvant activity. MUCOSAL IMMUNOLOGY. 2014;7(3):489–500.
MLA
Van Maele, L, D Fougeron, L Janot, et al. “Airway Structural Cells Regulate TLR5-mediated Mucosal Adjuvant Activity.” MUCOSAL IMMUNOLOGY 7.3 (2014): 489–500. Print.
@article{4397259,
  abstract     = {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.},
  author       = {Van Maele, L and Fougeron, D and Janot, L and Didierlaurent, A and Cayet, D and Tabareau, J and Rumbo, M and Corvo-Chamaillard, S and Boulenouar, S and Jeffs, S and Vande Walle, Lieselotte and Lamkanfi, Mohamed and Lemoine, Y and Erard, F and Hot, D and Hussell, T and Ryffel, B and Benecke, AG and Sirard, J-C},
  issn         = {1933-0219},
  journal      = {MUCOSAL IMMUNOLOGY},
  keyword      = {DENDRITIC CELLS,TOLL-LIKE RECEPTORS,IN-VIVO,BACTERIAL FLAGELLIN,CELLULAR MECHANISMS,NEGATIVE REGULATOR,LAMINA PROPRIA,INNATE IMMUNITY,ADAPTIVE IMMUNITY,INTESTINAL EPITHELIAL-CELLS},
  language     = {eng},
  number       = {3},
  pages        = {489--500},
  title        = {Airway structural cells regulate TLR5-mediated mucosal adjuvant activity},
  url          = {http://dx.doi.org/10.1038/mi.2013.66},
  volume       = {7},
  year         = {2014},
}

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