![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on February 1, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 5, 2003
Revised on October 3, 2003
Accepted on October 7, 2003
1 Departments of Medicine, University of California, San Francisco, San Francisco, California, 94143; School of Medicine, Yale University, 333 Cedar Street, New Haven CT 06520-8022
2 Departments of Anatomy, Biochemistry, and the Cardiovascular Research Institute University of California, San Francisco, San Francisco, California, 94143
3 Departments of Medicine, Microbiology and Immunology, Cardiovascular Research Institute University of California, San Francisco, San Francisco, California, 94143
* Corresponding author. E-mail address: Jengel{at}medicine.ucsf.edu.
Pseudomonas aeruginosa is an opportunistic human pathogen that preferentially infects damaged epithelial tissues. Previous studies have failed to distinguish whether the increased susceptibility of injured epithelium results from the loss of cell polarity or increased access to the basolateral surface. We have utilized confluent monolayers of Manin Darby Canine Kidney (MDCK) cells cultured on porous filter supports for 1-3 d as a model system to investigate whether the differentiation state of a polarized model epithelium affected the response of epithelial cells to this pathogen. Confluent incompletely polarized MDCK cell monolayers (day 1) efficiently internalized apically applied P. aeruginosa via a pathway that required actin polymerization and activation of Rho-family GTPases and was accompanied by an increase in the amount of activated RhoA. In contrast, P. aeruginosa entry into highly polarized MDCK monolayers (day 3) was 10-100-fold less efficient and was insensitive to inhibitors of actin polymerization or of Rho-family GTPase activation. There was no activation of RhoA; instead Cdc42-GTP levels increased significantly. Basolateral infection of highly polarized MDCK monolayers was less efficient and insensitive to Clostridium difficile Toxin B whereas basolateral infection of incompletely polarized MDCK monolayers was more efficient and required activation of Rho family GTPases. Together our findings suggest that as epithelial barrier differentiates and becomes highly polarized, it becomes resistant to P. aeruginosa infection. Nevetherless, polarized epithelial cells still sense the presence of apically infecting P. aeruginosa, but may do so through a different group of surface proteins and/or downstream signaling pathways than do incompletely polarized cells.
This article has been cited by other articles:
|
|
 |
|
  A. Kierbel, A. Gassama-Diagne, C. Rocha, L. Radoshevich, J. Olson, K. Mostov, and J. Engel Pseudomonas aeruginosa exploits a PIP3-dependent pathway to transform apical into basolateral membrane J. Cell Biol., April 9, 2007; 177(1): 21 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cuzick, F. R. Stirling, S. L. Lindsay, and T. J. Evans The Type III Pseudomonal Exotoxin U Activates the c-Jun NH2-Terminal Kinase Pathway and Increases Human Epithelial Interleukin-8 Production Infect. Immun., July 1, 2006; 74(7): 4104 - 4113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zulianello, C. Canard, T. Kohler, D. Caille, J.-S. Lacroix, and P. Meda Rhamnolipids Are Virulence Factors That Promote Early Infiltration of Primary Human Airway Epithelia by Pseudomonas aeruginosa. Infect. Immun., June 1, 2006; 74(6): 3134 - 3147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kierbel, A. Gassama-Diagne, K. Mostov, and J. N. Engel The Phosphoinositol-3-Kinase-Protein Kinase B/Akt Pathway Is Critical for Pseudomonas aeruginosa Strain PAK Internalization Mol. Biol. Cell, May 1, 2005; 16(5): 2577 - 2585. [Abstract] [Full Text] [PDF]
|
|
