Epithelial Uptake of Flagella Initiates Proinflammatory Signaling

Dane Parker, Alice Prince

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The airway epithelium serves multiple roles in the defense of the lung. Not only does it act as a physical barrier, it acts as a distal extension of the innate immune system. We investigated the role of the airway epithelium in the interaction with flagella, an important virulence factor of the pathogen Pseudomonas aeruginosa, a cause of ventilator associated pneumonia and significant morbidity and mortality in patients with cystic fibrosis. Flagella were required for transmigration across polarized airway epithelial cells and this was a direct consequence of motility, and not a signaling effect. Purified flagella did not alter the barrier properties of the epithelium but were observed to be rapidly endocytosed inside epithelial cells. Neither flagella nor intact P. aeruginosa stimulated epithelial inflammasome signaling. Flagella-dependent signaling required dynamin-based uptake as well as TLR5 and primarily led to the induction of proinflammatory (Tnf, Il6) as well as neutrophil (Cxcl1, Cxcl2, Ccl3) and macrophage (Ccl20) chemokines. Although flagella are important in invasion across the epithelial barrier their shedding in the airway lumen results in epithelial uptake and signaling that has a major role in the initial recruitment of immune cells in the lung.

Original languageEnglish (US)
Article numbere59932
JournalPloS one
Volume8
Issue number3
DOIs
StatePublished - Mar 20 2013

Fingerprint

Flagella
flagellum
uptake mechanisms
epithelium
Epithelium
Inflammasomes
Dynamins
Pseudomonas aeruginosa
Macrophages
Immune system
epithelial cells
Virulence Factors
Pathogens
Epithelial Cells
lungs
Chemokines
Ventilator-Associated Pneumonia
ventilators
Lung
Architectural Accessibility

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

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Epithelial Uptake of Flagella Initiates Proinflammatory Signaling. / Parker, Dane; Prince, Alice.

In: PloS one, Vol. 8, No. 3, e59932, 20.03.2013.

Research output: Contribution to journalArticle

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