Acid sphingomyelinase is involved in CEACAM receptor-mediated phagocytosis of Neisseria gonorrhoeae.
The interaction with human phagocytes is a hallmark of symptomatic Neisseria gonorrhoeae infections. Gonococcal outer membrane proteins of the Opa family induce the opsonin-independent uptake of the bacteria that relies on CEACAM receptors and an active signaling machinery of the phagocyte. Here, we show that CEACAM receptor-mediated phagocytosis of Opa(52)-expressing N. gonorrhoeae into human cells results in a rapid activation of the acid sphingomyelinase. Inhibition of this enzyme by imipramine or SR33557 abolishes opsonin-independent internalization without affecting bacterial adherence. Reconstitution of ceramide, the product of acid sphingomyelinase activity, in imipramine- or SR33557-treated cells restores internalization of the bacteria. Furthermore, we demonstrate that CEACAM receptor-initiated stimulation of other signalling molecules, in particular Src-like tyrosine kinases and Jun N-terminal kinases, requires acid sphingomyelinase. These studies provide evidence for a crucial role of the acid sphingomyelinase for CEACAM receptor-initiated signalling events and internalization of Opa(52)-expressing N. gonorrhoeae into human neutrophils.
Department of Physiology, University of Tübingen, Germany.
C R
CR
Hauck
H
H
Grassmé
J
J
Bock
V
V
Jendrossek
K
K
Ferlinz
T F
TF
Meyer
E
E
Gulbins
D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D007212:Indolizines / Q000494:pharmacology; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000276:immunology / Q000378:metabolism*; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002272:Carcinoembryonic Antigen; D002518:Ceramides; D007212:Indolizines; D010627:Phenethylamines; D011956:Receptors, Cell Surface; C050308:opacity proteins; D016392:Proto-Oncogene Proteins pp60(c-src); D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D013108:Sphingomyelin Phosphodiesterase; C059901:fantofarone; D007099:Imipramine