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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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
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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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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DOI: https://doi.org/10.1038/nm823
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