CD66-mediated phagocytosis of Opa52 Neisseria gonorrhoeae requires a Src-like tyrosine kinase- and Rac1-dependent signalling pathway.
The interaction of Neisseria gonorrhoeae with human phagocytes is a hallmark of gonococcal infections. Recently, CD66 molecules have been characterized as receptors for Opa52-expressing gonococci on human neutrophils. Here we show that Opa52-expressing gonococci or Escherichia coli or F(ab) fragments directed against CD66, respectively, activate a signalling cascade from CD66 via Src-like protein tyrosine kinases, Rac1 and PAK to Jun-N-terminal kinase. The induced signal is distinct from Fcgamma-receptor-mediated signalling and is specific for Opa52, since piliated Opa- gonococci, commensal Neisseria cinerea or E.coli do not stimulate this signalling pathway. Inhibition of Src-like kinases or Rac1 prevents the uptake of Opa52 bacteria, demonstrating the crucial role of this signalling cascade for the opsonin-independent, Opa52/CD66-mediated phagocytosis of pathogenic Neisseria.
Hauck
C R
CR
Max-Planck-Institut für Biologie, Abteilung Infektionsbiologie, Tübingen, Germany.
Meyer
T F
TF
Lang
F
F
Gulbins
E
E
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015815:Cell Adhesion Molecules; D004789:Enzyme Activation; D004790:Enzyme Induction; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007951:Leukemia, Myeloid; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D009344:Neisseria gonorrhoeae / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D009895:Opsonin Proteins; D010587:Phagocytosis; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051572:Proto-Oncogene Proteins c-hck; D015398:Signal Transduction; D013312:Stress, Physiological / Q000201:enzymology / Q000382:microbiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020744:rac GTP-Binding Proteins; D018909:src Homology Domains / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D009895:Opsonin Proteins; D011518:Proto-Oncogene Proteins; C090348:Opa protein, Neisseria; D014443:Tyrosine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins