title: Innate recognition by neutrophil granulocytes differs between Neisseria gonorrhoeae strains causing local or disseminating infections.
abstract: Members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family serve as cellular receptors for Neisseria gonorrhoeae. More specifically, neisserial colony opacity (OpaCEA)) proteins bind to epithelial CEACAMs (CEACAM1, CEA, CEACAM6) to promote bacterial colonization of the mucosa. In contrast, recognition by CEACAM3, expressed by human granulocytes, results in uptake and destruction of Opa(CEA)-expressing bacteria. Therefore, CEACAM3-mediated uptake might limit the spread of gonococci. However, some strains can cause disseminating gonococcal infections (DGIs), and it is currently unknown how these strains escape detection by granulocyte CEACAM3. Therefore, the opa gene loci from N. gonorrhoeae strain VP1, which was derived from a patient with disseminated gonococcal disease, were cloned and constitutively expressed in Escherichia coli. Similar to Opa proteins of the nondisseminating strain MS11, the majority of Opa proteins from strain VP1 bound epithelial CEACAMs and promoted CEACAM-initiated responses by epithelial cells. In sharp contrast to the Opa proteins of strain MS11, the Opa proteins of strain VP1 failed to interact with the human granulocyte receptor CEACAM3. Accordingly, bacteria expressing VP1 Opa proteins were not taken up by primary human granulocytes and did not trigger a strong oxidative burst. Analysis of Opa variants from four additional clinical DGI isolates again demonstrated a lack of CEACAM3 binding. In summary, our results reveal that particular N. gonorrhoeae strains express an Opa protein repertoire allowing engagement of epithelial CEACAMs for successful mucosal colonization, while avoiding recognition and elimination via CEACAM3-mediated phagocytosis. A failure of CEACAM3-mediated innate immune detection might be linked to the ability of gonococci to cause disseminated infections.
authors: Lehrstuhl für Zellbiologie, Universität Konstanz, Constance, Germany.
authors: Alexandra
authors: A
authors: Roth
authors: Corinna
authors: C
authors: Mattheis
authors: Petra
authors: P
authors: Muenzner
authors: Magnus
authors: M
authors: Unemo
authors: Christof R
authors: CR
authors: Hauck
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D056426:Genetic Loci; D006069:Gonorrhea / Q000276:immunology / Q000382:microbiology; D006098:Granulocytes / Q000276:immunology* / Q000382:microbiology; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000276:immunology / Q000472:pathogenicity*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D011485:Protein Binding; D013045:Species Specificity
chemical_list: D001425:Bacterial Outer Membrane Proteins; C075729:CEACAM3 protein, human; D002272:Carcinoembryonic Antigen; C090348:Opa protein, Neisseria
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