The CGM1a (CEACAM3/CD66d)-mediated phagocytic pathway of Neisseria gonorrhoeae expressing opacity proteins is also the pathway to cell death.
Phagocytosis of Opa+ Neisseria gonorrhoeae (gonococcus, GC) by neutrophils is in part dependent on the interaction of Opa proteins with CGM1a (CEACAM3/CD66d) antigens, a neutrophil-specific receptor. However, the signaling pathways leading to phagocytosis have not been characterized. Here we show that interaction of OpaI bacteria with neutrophils or CGM1a-transfected DT40 cells induces calcium flux, which correlates with phagocytosis of bacteria. We identified an immunoreceptor tyrosine-based activation motif (ITAM) in CGM1a, and showed that the ability of CGM1a to transduce signals and mediate phagocytosis was abolished by mutation of the ITAM tyrosines. We also demonstrated that CGM1a-ITAM-mediated bacterial phagocytosis is dependent on Syk and phospholipase C activity in DT40 cells. Unexpectedly, the activation of the CGM1a-ITAM phagocytic pathway by Opa+ GC results in induction of cell death.
Department of Microbiology, Immunology and Medicine, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. tiechen@iupui.edu
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Chen
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Bolland
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Parker
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Pantelic
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Grunert
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Zimmermann
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D002118:Calcium / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002645:Chickens; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000502:physiology*; D009504:Neutrophils / Q000382:microbiology* / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D000072377:Syk Kinase; D014162:Transfection
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C075729:CEACAM3 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C090348:Opa protein, Neisseria; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D002118:Calcium