Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts
- PMID: 12563314
- DOI: 10.1038/nm823
Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts
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.
Similar articles
-
Acid sphingomyelinase amplifies redox signaling in Pseudomonas aeruginosa-induced macrophage apoptosis.J Immunol. 2008 Sep 15;181(6):4247-54. doi: 10.4049/jimmunol.181.6.4247. J Immunol. 2008. PMID: 18768882
-
Regulation of Pseudomonas aeruginosa internalization after contact lens wear in vivo and in serum-free culture by ocular surface cells.Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3430-40. doi: 10.1167/iovs.05-1332. Invest Ophthalmol Vis Sci. 2006. PMID: 16877413
-
Localization of cystic fibrosis transmembrane conductance regulator to lipid rafts of epithelial cells is required for Pseudomonas aeruginosa-induced cellular activation.J Immunol. 2004 Jan 1;172(1):418-25. doi: 10.4049/jimmunol.172.1.418. J Immunol. 2004. PMID: 14688350
-
Ceramide in bacterial infections and cystic fibrosis.Biol Chem. 2008 Nov;389(11):1371-9. doi: 10.1515/BC.2008.162. Biol Chem. 2008. PMID: 18783339 Review.
-
Biological aspects of ceramide-enriched membrane domains.Prog Lipid Res. 2007 May-Jul;46(3-4):161-70. doi: 10.1016/j.plipres.2007.03.002. Epub 2007 Mar 31. Prog Lipid Res. 2007. PMID: 17490747 Review.
Cited by
-
Cyclodextrins reduce the ability of Pseudomonas aeruginosa outer-membrane vesicles to reduce CFTR Cl- secretion.Am J Physiol Lung Cell Mol Physiol. 2019 Jan 1;316(1):L206-L215. doi: 10.1152/ajplung.00316.2018. Epub 2018 Oct 25. Am J Physiol Lung Cell Mol Physiol. 2019. PMID: 30358440 Free PMC article.
-
Pseudomonas aeruginosa and sPLA2 IB stimulate ABCA1-mediated phospholipid efflux via ERK-activation of PPARalpha-RXR.Biochem J. 2007 May 1;403(3):409-20. doi: 10.1042/BJ20061364. Biochem J. 2007. PMID: 17223797 Free PMC article.
-
Menthone Exerts its Antimicrobial Activity Against Methicillin Resistant Staphylococcus aureus by Affecting Cell Membrane Properties and Lipid Profile.Drug Des Devel Ther. 2023 Jan 25;17:219-236. doi: 10.2147/DDDT.S384716. eCollection 2023. Drug Des Devel Ther. 2023. PMID: 36721663 Free PMC article.
-
Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation.Front Immunol. 2019 Feb 26;10:109. doi: 10.3389/fimmu.2019.00109. eCollection 2019. Front Immunol. 2019. PMID: 30863392 Free PMC article.
-
The Role of Lipids in the Regulation of Immune Responses.Nutrients. 2023 Sep 7;15(18):3899. doi: 10.3390/nu15183899. Nutrients. 2023. PMID: 37764683 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases