title: Epithelial uptake of flagella initiates proinflammatory signaling.
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.
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York, United States of America. dp2375@columbia.edu
authors.forename: Dane
authors.initials: D
authors.lastname: Parker
authors.forename: Alice
authors.initials: A
authors.lastname: Prince
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005407:Flagella / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D018613:Microscopy, Confocal; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D037521:Virulence Factors
chemical_list: D000911:Antibodies, Monoclonal; D017931:DNA Primers; D037521:Virulence Factors