Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts.
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.
Grassmé
H
H
Department of Molecular Biology, University of Essen, Essen, Germany.
Jendrossek
V
V
Riehle
A
A
von Kürthy
G
G
Berger
J
J
Schwarz
H
H
Weller
M
M
Kolesnick
R
R
Gulbins
E
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D003505:Cyclodextrins / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005372:Filipin / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009761:Nystatin / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D047392:beta-Cyclodextrins; D019014:fas Receptor / Q000378:metabolism
C505032:CFTR protein, human; D002518:Ceramides; D003505:Cyclodextrins; D005456:Fluorescent Dyes; D007476:Ionophores; D047392:beta-Cyclodextrins; D019014:fas Receptor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D009761:Nystatin; D005372:Filipin; D013108:Sphingomyelin Phosphodiesterase; C031215:betadex