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Article
Nature Medicine  9, 322 - 330 (2003)
Published online: 3 February 2003; Corrected online: 10 February 2003 | doi:10.1038/nm823

Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts

H. Grassmé1, V. Jendrossek2, A. Riehle1, G. von Kürthy3, J. Berger4, H. Schwarz4, M. Weller3, R. Kolesnick5 & E. Gulbins1

1  Department of Molecular Biology, University of Essen, Essen, Germany

2  Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany

3  Department of Neurology, University of Tuebingen, Tuebingen, Germany

4  Max-Planck Institute for Developmental Biology, Tuebingen, Germany

5  Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Correspondence should be addressed to E. Gulbins erich.gulbins@uni-essen.de
Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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