Previous Article | Next Article 
Infection and Immunity, May 2003, p. 2665-2673, Vol. 71, No. 5
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.5.2665-2673.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Apoptotic Response of Chang Cells to Infection with Pseudomonas aeruginosa Strains PAK and PAO-I: Molecular Ordering of the Apoptosis Signaling Cascade and Role of Type IV Pili
Verena Jendrossek,1* Sophie Fillon,1 Claus Belka,2 Ilka Müller,1 Beatrice Puttkammer,1 and Florian Lang1
Department of Physiology,1
Department of Radiation Oncology, University of Tübingen, 72076 Tübingen, Germany2
Received 24 July 2002/
Returned for modification 26 September 2002/
Accepted 16 January 2003
Pseudomonas aeruginosa is a gram-negative facultative opportunistic pathogen associated with severe infections in immunocompromised hosts and in patients with cystic fibrosis. P. aeruginosa strains show divergent pathogenicity in vivo and trigger apoptosis of and/or are internalized into human host cells. In the present study, we studied the molecular ordering of apoptosis signaling upon infection of human conjunctiva epithelial Chang cells with P. aeruginosa PAK as well as the role of bacterial pili in the response to the infection. Our results show that CD95 up-regulation is followed by early activation of caspase-8 and -3 and cleavage of the caspase-3 substrate poly(ADP-ribose) polymerase. The data also demonstrate release of apoptosis inducing factor into the cytosol of infected cells. Induction of mitochondrial alterations, i.e., mitochondrial depolarization and release of cytochrome c, as well as cleavage of caspase-9, -7, and -1 occurred only at later time points. In addition, our results demonstrate that pili are required for P. aeruginosa-induced apoptosis of human epithelial cells. While the two piliated P. aeruginosa strains, PAO-I and PAK, induced apoptosis of Chang cells within 3 h of infection, the pilus-deficient P. aeruginosa mutants PAK
pilA and PAK
pilA
all were without effect. The pilus-deficient mutants failed to induce a significant up-regulation of CD95 on the cell surface and to trigger mitochondrial alterations or activation of caspase-8, -3, and -7. In addition, only the piliated wild-type strains induced caspase-1-mediated activation of interleukin-1ß. Thus, pili are necessary for distinct infection-induced cellular responses of human epithelial cells.
* Corresponding author. Present address: Dept. of Radiation Oncology, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany. Phone: 49-7071-2985961. Fax: 49-7071-294944. E-mail:
verena.jendrossek{at}uni-tuebingen.de.
Editor: V. J. DiRita
Infection and Immunity, May 2003, p. 2665-2673, Vol. 71, No. 5
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.5.2665-2673.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Alarcon, I., Evans, D. J., Fleiszig, S. M. J.
(2009). The Role of Twitching Motility in Pseudomonas aeruginosa Exit from and Translocation of Corneal Epithelial Cells. IOVS
50: 2237-2244
[Abstract]
[Full Text]
-
Holden, M. T. G., Seth-Smith, H. M. B., Crossman, L. C., Sebaihia, M., Bentley, S. D., Cerdeno-Tarraga, A. M., Thomson, N. R., Bason, N., Quail, M. A., Sharp, S., Cherevach, I., Churcher, C., Goodhead, I., Hauser, H., Holroyd, N., Mungall, K., Scott, P., Walker, D., White, B., Rose, H., Iversen, P., Mil-Homens, D., Rocha, E. P. C., Fialho, A. M., Baldwin, A., Dowson, C., Barrell, B. G., Govan, J. R., Vandamme, P., Hart, C. A., Mahenthiralingam, E., Parkhill, J.
(2009). The Genome of Burkholderia cenocepacia J2315, an Epidemic Pathogen of Cystic Fibrosis Patients. J. Bacteriol.
191: 261-277
[Abstract]
[Full Text]
-
Sutterwala, F. S., Mijares, L. A., Li, L., Ogura, Y., Kazmierczak, B. I., Flavell, R. A.
(2007). Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. JEM
204: 3235-3245
[Abstract]
[Full Text]
-
Jia, J., Wang, Y., Zhou, L., Jin, S.
(2006). Expression of Pseudomonas aeruginosa Toxin ExoS Effectively Induces Apoptosis in Host Cells. Infect. Immun.
74: 6557-6570
[Abstract]
[Full Text]
-
Kirschnek, S., Gulbins, E.
(2006). Phospholipase A2 Functions in Pseudomonas aeruginosa- Induced Apoptosis. Infect. Immun.
74: 850-860
[Abstract]
[Full Text]
-
Cobb, L. M., Mychaleckyj, J. C., Wozniak, D. J., Lopez-Boado, Y. S.
(2004). Pseudomonas aeruginosa Flagellin and Alginate Elicit Very Distinct Gene Expression Patterns in Airway Epithelial Cells: Implications for Cystic Fibrosis Disease. J. Immunol.
173: 5659-5670
[Abstract]
[Full Text]
-
Zhou, H., Lu, F., Latham, C., Zander, D. S., Visner, G. A.
(2004). Heme Oxygenase-1 Expression in Human Lungs with Cystic Fibrosis and Cytoprotective Effects against Pseudomonas Aeruginosa In Vitro. Am. J. Respir. Crit. Care Med.
170: 633-640
[Abstract]
[Full Text]