{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:34:57Z","timestamp":1785429297456,"version":"3.56.0"},"reference-count":23,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["DE023071-07"],"award-info":[{"award-number":["DE023071-07"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["DE032119"],"award-info":[{"award-number":["DE032119"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DE023071-07"],"award-info":[{"award-number":["DE023071-07"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DE032119"],"award-info":[{"award-number":["DE032119"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Grade C molar-incisor pattern periodontitis (C-MIP) is a rapidly progressive form of periodontal disease affecting young individuals that is often linked to a highly virulent genotype of Aggregatibacter actinomycetemcomitans (Aa). Although Aa is present in the healthy oral microbiome, its transition into subgingival tissue correlates with the conversion from healthy to diseased status within the periodontal pocket. These changes may be due to immune evasion strategies attributed to Aa exotoxins. We previously demonstrated that a host cell protein, cellugyrin, plays a critical role in exotoxin internalization and subsequent cytotoxicity. Herein, we assess the contribution of cellugyrin to Aa phagocytosis and intracellular trafficking in human macrophages. Confocal imaging demonstrated that Aa co-localizes with cellugyrin. Importantly, cellugyrin-deficient macrophages exhibited a significant reduction in phagocytosed Aa. Furthermore, we analyzed the role of retrograde trafficking in Aa survival. Retro-2-mediated inhibition of this trafficking pathway resulted in increased intracellular Aa, likely due to increased survival. Collectively, our findings suggest that cellugyrin is involved in Aa phagocytosis and that retrograde trafficking may play a role in subsequent host cell clearance of Aa.<\/jats:p>","DOI":"10.3390\/pathogens15050505","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:11:13Z","timestamp":1778271073000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellugyrin (Synaptogyrin-2) Regulates Macrophage Phagocytosis of Aggregatibacter actinomycetemcomitans (Aa)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7100-4576","authenticated-orcid":false,"given":"Taewan J.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleena","family":"Defreitas","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa P.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Shenker","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0962-0508","authenticated-orcid":false,"given":"Kathleen","family":"Boesze-Battaglia","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/prd.12020","article-title":"Treatment of aggressive periodontitis","volume":"65","author":"Teughels","year":"2014","journal-title":"Periodontology 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J. 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