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A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa
Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we s...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388098/ https://www.ncbi.nlm.nih.gov/pubmed/22768318 http://dx.doi.org/10.1371/journal.pone.0039888 |
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author | Mohamed, Fatima Ben Garcia-Verdugo, Ignacio Medina, Mathieu Balloy, Viviane Chignard, Michel Ramphal, Reuben Touqui, Lhousseine |
author_facet | Mohamed, Fatima Ben Garcia-Verdugo, Ignacio Medina, Mathieu Balloy, Viviane Chignard, Michel Ramphal, Reuben Touqui, Lhousseine |
author_sort | Mohamed, Fatima Ben |
collection | PubMed |
description | Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis. |
format | Online Article Text |
id | pubmed-3388098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33880982012-07-05 A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa Mohamed, Fatima Ben Garcia-Verdugo, Ignacio Medina, Mathieu Balloy, Viviane Chignard, Michel Ramphal, Reuben Touqui, Lhousseine PLoS One Research Article Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis. Public Library of Science 2012-07-02 /pmc/articles/PMC3388098/ /pubmed/22768318 http://dx.doi.org/10.1371/journal.pone.0039888 Text en Ben Mohamed et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mohamed, Fatima Ben Garcia-Verdugo, Ignacio Medina, Mathieu Balloy, Viviane Chignard, Michel Ramphal, Reuben Touqui, Lhousseine A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa |
title | A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa
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title_full | A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa
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title_fullStr | A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa
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title_full_unstemmed | A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa
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title_short | A Crucial Role of Flagellin in the Induction of Airway Mucus Production by Pseudomonas aeruginosa
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title_sort | crucial role of flagellin in the induction of airway mucus production by pseudomonas aeruginosa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388098/ https://www.ncbi.nlm.nih.gov/pubmed/22768318 http://dx.doi.org/10.1371/journal.pone.0039888 |
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