CD66 carcinoembryonic antigens mediate interactions between Opa-expressing Neisseria gonorrhoeae and human polymorphonuclear phagocytes.
Colonization of urogenital tissues by the human pathogen Neisseria gonorrhoeae is characteristically associated with purulent exudates of polymorphonuclear phagocytes (PMNs) containing apparently viable bacteria. Distinct variant forms of the phase-variable opacity-associated (Opa) outer membrane proteins mediate the non-opsonized binding and internalization of N. gonorrhoeae by human PMNs. Using overlay assays and an affinity isolation technique, we demonstrate the direct interaction between Opa52-expressing gonococci and members of the human carcinoembryonic antigen (CEA) family which express the CD66 epitope. Gonococci and recombinant Escherichia coli strains synthesizing Opa52 showed specific binding and internalization by transfected HeLa cell lines expressing the CD66 family members BGP (CD66a), NCA (CD66c), CGM1 (CD66d) and CEA (CD66e), but not that expressing CGM6 (CD66b). Bacterial strains expressing either no opacity protein or the epithelial cell invasion-associated Opa50 do not bind these CEA family members. Consistent with their different receptor specificities, Opa52-mediated interactions could be inhibited by polyclonal anti-CEA sera, while Opa50 binding was instead inhibited by heparin. Using confocal laser scanning microscopy, we observed a marked recruitment of CD66 antigen by Opa52-expressing gonococci on both the transfected cell lines and infected PMNs. These data indicate that members of the CEA family constitute the cellular receptors for the interaction with, and internalization of, N. gonorrhoeae.
Gray-Owen
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SD
Max-Planck-Institut für Biologie, Abteilung Infektionsbiologie, Tübingen, Germany.
Dehio
C
C
Haude
A
A
Grunert
F
F
Meyer
T F
TF
D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D000939:Epitopes / Q000378:metabolism; D004926:Escherichia coli; D058851:GPI-Linked Proteins; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D011995:Recombination, Genetic; D014162:Transfection
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; C069847:CD66 antigens; C075729:CEACAM3 protein, human; C504117:CEACAM6 protein, human; C504120:CEACAM8 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D000939:Epitopes; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C050308:opacity proteins