{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:49:41Z","timestamp":1787496581273,"version":"build-2736575974"},"posted":{"date-parts":[[2026,1,20]]},"group-title":"Microbiology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01AI097312"],"award-info":[{"award-number":["R01AI097312"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31AI188753"],"award-info":[{"award-number":["F31AI188753"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32AI007046"],"award-info":[{"award-number":["T32AI007046"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31AI157528"],"award-info":[{"award-number":["F31AI157528"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R41AI179576"],"award-info":[{"award-number":["R41AI179576"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R43AI186979"],"award-info":[{"award-number":["R43AI186979"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Wagner Fellowship"],"award-info":[{"award-number":["Wagner Fellowship"]}],"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30CA044579"],"award-info":[{"award-number":["P30CA044579"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1S10OD028518"],"award-info":[{"award-number":["1S10OD028518"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1S10OD034355"],"award-info":[{"award-number":["1S10OD034355"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                  (Gc) causes the sexually transmitted infection gonorrhea, an urgent public health concern. Gc infection elicits a robust neutrophil response and serum leakage, but Gc has developed specialized defenses to evade both complement and neutrophils. We recently reported that the classical complement pathway inhibitor C4b-binding protein (C4BP) binds to Gc and reduces phagocytic killing by neutrophils in a complement-independent manner. Here, we used a Chinese hamster ovary (CHO) expression system and engineered C4BP constructs to define the underlying molecular mechanisms. C4BP inhibited interactions between opacity protein (Opa)-expressing Gc and carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), receptors that drive non-opsonic phagocytosis of Gc by neutrophils. The degree of C4BP-mediated inhibition varied among CEACAMs. By using wild-type and chimeric CEACAMs, we found C4BP was more inhibitory towards the granulocyte-restricted CEACAM3 than the ubiquitously expressed CEACAM1, which we ascribed to CEACAM3\u2019s shorter extracellular domain. C4BP also inhibited the association between Opa-expressing Gc and the GPI-anchored CEACAM6. Molecules containing C4BP domains 1 and 2 fused to IgM (C4BP-IgM) or to a hexameric IgG Fc construct (C4BP-Hexa-IgG), proteins similar in diameter and degree of multimerization to native C4BP, inhibited the association of Opa-expressing Gc with CEACAM3-CHO cells to the same degree as C4BP, while C4BP domains 1 and 2 fused to dimeric Fc (C4BP-IgG) did not. C4BP-IgM, but not C4BP-IgG bearing mutations to abrogate Fc gamma receptor interactions, blocked Opa-mediated phagocytosis by primary human neutrophils. These results support a model in which C4BP occludes Opa-CEACAM interactions, which protects Gc from phagocytic killing by neutrophils.\n                <\/jats:p>","DOI":"10.64898\/2026.01.19.700458","type":"posted-content","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T17:10:12Z","timestamp":1768929012000},"source":"Crossref","is-referenced-by-count":1,"title":["C4BP occludes the non-opsonic interaction of\n                  <i>Neisseria gonorrhoeae<\/i>\n                  with human neutrophil CEACAMs"],"prefix":"10.64898","author":[{"given":"Mary W.","family":"Broden","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutamas","family":"Shaughnessy","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida","family":"Mohlin","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaris J.","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison K.","family":"Criss","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of 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