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Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts

Nature Medicine volume 9, pages 322–330 (2003)Cite this article

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Abstract

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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Figure 1: CFTR and CD95 cluster in sphingolipid-rich membrane platforms after infection with P. aeruginosa.
Figure 2: Sphingolipid-rich rafts are essential for P. aeruginosa infection of mammalian cells.
Figure 3: P. aeruginosa triggers platform formation by ASM-mediated release of ceramide.
Figure 4: ASM and ceramide-enriched membrane platforms regulate host cell apoptosis, P. aeruginosa internalization and cytokine release.
Figure 5: ASM is central to host defense against P. aeruginosa.

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Change history

  • 10 February 2003

    This was incorrect in AOP version but corrected in print. Regplaced Figure 1 and Figure 3 as per note.

Notes

  1. NOTE: In the version of this article initially published online, the labels for Figs. 1 and 3d were incorrect. The upper left label of Fig. 1a should read 'not infected'. All labels that read 'TEM' should read 'transmission'. This mistake has been corrected for the HTML and print versions of the article.

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Acknowledgements

E.G. was supported in part by the Deutsche Forschungsgemeinschaft (Gu 335/10-2 and Mo 435/17-1); the European Union; the Association for International Cancer Research; the National Cancer Institute (CA21765); and American Lebanese Syrian Associated Charities. M.W. was supported by the Deutsche Forschungsgemeinschaft (We 1502/10-1). R.K. was supported by the National Cancer Institute (CA85704).

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Authors and Affiliations

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

    H. Grassmé, A. Riehle & E. Gulbins

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

    V. Jendrossek

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

    G. von Kürthy & M. Weller

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

    J. Berger & H. Schwarz

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

    R. Kolesnick

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Correspondence to E. Gulbins.

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Grassmé, H., Jendrossek, V., Riehle, A. et al. Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat Med 9, 322–330 (2003). https://doi.org/10.1038/nm823

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