Carcinoembryonic antigen family receptor specificity of Neisseria meningitidis Opa variants influences adherence to and invasion of proinflammatory cytokine-activated endothelial cells.
The carcinoembryonic antigen (CEA) family member CEACAM1 (previously called biliary glycoprotein or CD66a) was previously shown to function as a receptor that can mediate the binding of Opa protein-expressing Neisseria meningitidis to both neutrophils and epithelial cells. Since neutrophils and polarized epithelia have both been shown to coexpress multiple CEACAM receptors, we have now extended this work to characterize the binding specificity of meningococcal Opa proteins with other CEA family members. To do so, we used recombinant Escherichia coli expressing nine different Opa variants from three meningococcal strains and stably transfected cell lines expressing single members of the CEACAM family. These infection studies demonstrated that seven of the nine Opa variants bound to at least one CEACAM receptor and that binding to each of these receptors is sufficient to trigger the Opa-dependent bacterial uptake by these cell lines. The other two Opa variants do not appear to bind to either CEACAM receptors or heparan sulfate proteoglycan receptors, which are bound by some gonococcal Opa variants, thus implying a novel class of Opa proteins. We have also extended previous studies by demonstrating induction of CEACAM1 expression after stimulation of human umbilical vein endothelial cells with the proinflammatory cytokine tumor necrosis factor alpha, which is present in high concentrations during meningococcal disease. This induced expression of CEACAM1 leads to an increased Opa-dependent bacterial binding and invasion into the primary endothelia, implying that these interactions may play an important role in the pathogenesis of invasive meningococcal disease.
Muenzner
P
P
Abteilung, Infektionsbiologie, Max-Planck-Institut für Biologie, 72076 Tübingen, Germany.
Dehio
C
C
Fujiwara
T
T
Achtman
M
M
Meyer
T F
TF
Gray-Owen
S D
SD
D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D016207:Cytokines; D004730:Endothelium, Vascular / Q000187:drug effects / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C050308:opacity proteins