Published ahead of print on November 7, 2003, doi:10.1165/rcmb.2003-0260OC
American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 627-634, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0260OC
Pseudomonas aeruginosa Flagella Activate Airway Epithelial Cells through asialoGM1 and Toll-Like Receptor 2 as well as Toll-Like Receptor 5
Robert Adamo,
Sach Sokol,
Grace Soong,
Marisa I. Gomez and
Alice Prince
Departments of Pediatrics and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York
Address correspondence to: Alice Prince, Departments of Pediatrics and Pharmacology, College of Physicians and Surgeons, Columbia University, BB 416–650 W. 168th Street, New York, NY 10032. E-mail: asp7{at}columbia.edu
The distribution of specific toll-like receptors and components of the signaling pathways activated by Pseudomonas aeruginosa flagella were studied in airway epithelial cells. Initially flagella bound to the apical surface of polarized epithelial cells, where they prominently colocalized with asialoGM1. By 4 h of exposure to flagella, toll-like receptor (TLR)5 expression was induced, mobilized to the apical surface of the cells, and colocalized with superficial flagella. Interleukin-8 expression in airway cells was activated by flagella through induction of Ca2+ fluxes, Src, Ras, and extracellular signal–regulated kinase 1/2 mitogen-activated protein kinase and nuclear factor- B activation, a pathway previously associated with asialoGM1-mediated stimuli. There was evidence for participation of asialoGM1 and TLR2 as well as TLR5 in the response to flagella, and increased asialoGM1 correlated directly with increased signaling. TLR2 DN or TLR5 DN mutations inhibited interleukin-8 induction by 78% and 35%, respectively (P < 0.001 for each). The participation of TLR2 as well as TLR5 was confirmed in Chinese hamster ovary cells transfected with either human TLR2 or TLR5 in which flagella activated a nuclear factor-B–luciferase reporter to the same extent. Flagella signaling in airway cells can be initiated by interactions with asialoGM1 and TLR2 as well as by activation of TLR5. The availability of exposed receptors on the apical surface of polarized airway epithelial cells is a major factor in the activation of signaling pathways by flagella.
Abbreviations: gangliotetraosylceramide (Galß1,2GalNAcß1,4Galß1,4Glcß1,1Cer), asialoGM1 • 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid, BAPTA • Chinese hamster ovary, CHO • Dulbecco's modified Eagle's media, DMEM • enzyme-linked immunosorbent assay, ELISA • extracellular signal–regulated kinases(s), ERK(s) • fetal calf serum, FCS • interleukin, IL • interleukin-1 receptor–activated kinase, IRAK • lipopolysaccharide, LPS • mitogen-activated protein kinases, MAPKs • mass spectroscopy, MS • normal human nasal polyp, NHNP • phosphate-buffered saline, PBS • toll-like receptor, TLR
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|
|
|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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292(1):
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|
|
|
|
|
|
|
Z. Fu, K. Bettega, S. Carroll, K. R. Buchholz, and T. E. Machen
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292(1):
L353 - L364.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sonawane, J. Jyot, R. During, and R. Ramphal
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December 1, 2006;
74(12):
6682 - 6689.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Du, F. Zhang, J. E. Capo-Aponte, S. D. Tachado, J. Zhang, F.-S. X. Yu, R. A. Sack, H. Koziel, and P. S. Reinach
AsialoGM1-Mediated IL-8 Release by Human Corneal Epithelial Cells Requires Coexpression of TLR5
Invest. Ophthalmol. Vis. Sci.,
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47(11):
4810 - 4818.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Feuillet, S. Medjane, I. Mondor, O. Demaria, P. P. Pagni, J. E. Galan, R. A. Flavell, and L. Alexopoulou
Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria
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August 15, 2006;
103(33):
12487 - 12492.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Machen
Innate immune response in CF airway epithelia: hyperinflammatory?
Am J Physiol Cell Physiol,
August 1, 2006;
291(2):
C218 - C230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chun and A. Prince
Activation of Ca2+-Dependent Signaling by TLR2
J. Immunol.,
July 15, 2006;
177(2):
1330 - 1337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Dehus, T. Hartung, and C. Hermann
Endotoxin evaluation of eleven lipopolysaccharides by whole blood assay does not always correlate with Limulus amebocyte lysate assay
Innate Immunity,
June 1, 2006;
12(3):
171 - 180.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. McNamara, M. Gallup, A. Sucher, I. Maltseva, D. McKemy, and C. Basbaum
AsialoGM1 and TLR5 Cooperate in Flagellin-Induced Nucleotide Signaling to Activate Erk1/2
Am. J. Respir. Cell Mol. Biol.,
June 1, 2006;
34(6):
653 - 660.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Delgado, J. F. Poschet, and V. Deretic
Nonclassical Pathway of Pseudomonas aeruginosa DNA-Induced Interleukin-8 Secretion in Cystic Fibrosis Airway Epithelial Cells.
Infect. Immun.,
May 1, 2006;
74(5):
2975 - 2984.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Prince
Flagellar Activation of Epithelial Signaling
Am. J. Respir. Cell Mol. Biol.,
May 1, 2006;
34(5):
548 - 551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Sadikot, H. Zeng, M. Joo, M. B. Everhart, T. P. Sherrill, B. Li, D.-s. Cheng, F. E. Yull, J. W. Christman, and T. S. Blackwell
Targeted Immunomodulation of the NF-{kappa}B Pathway in Airway Epithelium Impacts Host Defense against Pseudomonas aeruginosa.
J. Immunol.,
April 15, 2006;
176(8):
4923 - 4930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Swiatecka-Urban, S. Moreau-Marquis, D. P. MacEachran, J. P. Connolly, C. R. Stanton, J. R. Su, R. Barnaby, G. A. O'Toole, and B. A. Stanton
Pseudomonas aeruginosa inhibits endocytic recycling of CFTR in polarized human airway epithelial cells
Am J Physiol Cell Physiol,
March 1, 2006;
290(3):
C862 - C872.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Tseng, J. Do, J. H. Widdicombe, and T. E. Machen
Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-{alpha}, and IL-1beta
Am J Physiol Cell Physiol,
March 1, 2006;
290(3):
C678 - C690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Verma, S. K. Arora, S. K. Kuravi, and R. Ramphal
Roles of Specific Amino Acids in the N Terminus of Pseudomonas aeruginosa Flagellin and of Flagellin Glycosylation in the Innate Immune Response
Infect. Immun.,
December 1, 2005;
73(12):
8237 - 8246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-M. Chen, S. P. O'Hara, J. B. Nelson, P. L. Splinter, A. J. Small, P. S. Tietz, A. H. Limper, and N. F. LaRusso
Multiple TLRs Are Expressed in Human Cholangiocytes and Mediate Host Epithelial Defense Responses to Cryptosporidium parvum via Activation of NF-{kappa}B
J. Immunol.,
December 1, 2005;
175(11):
7447 - 7456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Zhang, J.-P. Louboutin, D. J. Weiner, J. B. Goldberg, and J. M. Wilson
Human Airway Epithelial Cells Sense Pseudomonas aeruginosa Infection via Recognition of Flagellin by Toll-Like Receptor 5
Infect. Immun.,
November 1, 2005;
73(11):
7151 - 7160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Lane, V. Lockatell, G. Monterosso, D. Lamphier, J. Weinert, J. R. Hebel, D. E. Johnson, and H. L. T. Mobley
Role of Motility in the Colonization of Uropathogenic Escherichia coli in the Urinary Tract
Infect. Immun.,
November 1, 2005;
73(11):
7644 - 7656.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Hajjar, H. Harowicz, H. D. Liggitt, P. J. Fink, C. B. Wilson, and S. J. Skerrett
An Essential Role for Non-Bone Marrow-Derived Cells in Control of Pseudomonas aeruginosa Pneumonia
Am. J. Respir. Cell Mol. Biol.,
November 1, 2005;
33(5):
470 - 475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Molofsky, L. M. Shetron-Rama, and M. S. Swanson
Components of the Legionella pneumophila Flagellar Regulon Contribute to Multiple Virulence Traits, Including Lysosome Avoidance and Macrophage Death
Infect. Immun.,
September 1, 2005;
73(9):
5720 - 5734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. Gomez, S. H. Sokol, A. B. Muir, G. Soong, J. Bastien, and A. S. Prince
Bacterial Induction of TNF-{alpha} Converting Enzyme Expression and IL-6 Receptor {alpha} Shedding Regulates Airway Inflammatory Signaling
J. Immunol.,
August 1, 2005;
175(3):
1930 - 1936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Sadikot, T. S. Blackwell, J. W. Christman, and A. S. Prince
Pathogen-Host Interactions in Pseudomonas aeruginosa Pneumonia
Am. J. Respir. Crit. Care Med.,
June 1, 2005;
171(11):
1209 - 1223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Miller, O. E. Sorensen, P. T. Liu, H. R. Jalian, D. Eshtiaghpour, B. E. Behmanesh, W. Chung, T. D. Starner, J. Kim, P. A. Sieling, et al.
TGF-{alpha} Regulates TLR Expression and Function on Epidermal Keratinocytes
J. Immunol.,
May 15, 2005;
174(10):
6137 - 6143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Power, Y. Peng, E. Maydanski, J. S. Marshall, and T.-J. Lin
The Development of Early Host Response to Pseudomonas aeruginosa Lung Infection Is Critically Dependent on Myeloid Differentiation Factor 88 in Mice
J. Biol. Chem.,
November 19, 2004;
279(47):
49315 - 49322.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Cobb, J. C. Mychaleckyj, D. J. Wozniak, and Y. S. Lopez-Boado
Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease
J. Immunol.,
November 1, 2004;
173(9):
5659 - 5670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lorenz, D. C. Chemotti, K. Vandal, and P. A. Tessier
Toll-Like Receptor 2 Represses Nonpilus Adhesin-Induced Signaling in Acute Infections with the Pseudomonas aeruginosa pilA Mutant
Infect. Immun.,
August 1, 2004;
72(8):
4561 - 4569.
[Abstract]
[Full Text]
[PDF]
|
|
|
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