{"doi":"10.1038/icb.2013.35","title":"A periodontal pathogen <i>Treponema denticola</i> hijacks the <i>Fusobacterium nucleatum</i>‐driven host response","abstract":"<jats:p>Periodontitis is a polymicrobial disease that arises from the dysbiosis of the plaque biofilm. To study polymicrobial interactions with gingival epithelial cells, the oral commensal <jats:italic>Fusobacterium nucleatum</jats:italic> and the periodontal pathogen <jats:italic>Treponema denticola</jats:italic> were chosen due to their opposing effects on the expression of human beta‐defensins (HBDs) and interleukin (IL)‐8 in gingival epithelial cells. Immortalized gingival epithelial HOK‐16B cells were infected with either <jats:italic>F. nucleatum</jats:italic> or <jats:italic>T. denticola</jats:italic> alone or together, and the expression of HBDs and IL‐8 was investigated. Coinfection with <jats:italic>F. nucleatum</jats:italic> and <jats:italic>T. denticola</jats:italic> neutralized the stimulatory and suppressive effects on the expression of HBD‐2 and ‐3, but the suppressive effect of <jats:italic>T. denticola</jats:italic> on IL‐8 expression remained. In CHO/CD14/TLR2 reporter cells, <jats:italic>T. denticola</jats:italic> attenuated <jats:italic>F. nucleatum</jats:italic>‐induced activation of TLR2, a receptor that mediates HBD induction. Although <jats:italic>F. nucleatum</jats:italic> facilitated the invasion of <jats:italic>T. denticola</jats:italic> into host cells, <jats:italic>T. denticola</jats:italic> interfered with the fusion of internalized <jats:italic>F. nucleatum</jats:italic> with lysosomes, which may avert TLR9‐dependent IL‐8 induction. Furthermore, <jats:italic>T. denticola</jats:italic> suppressed the <jats:italic>F. nucleatum</jats:italic>‐stimulated accumulation of intracellular reactive oxygen species (ROS), a group of essential signaling molecules for the TLR2 and TLR9 pathways. The elimination of ROS using <jats:italic>N</jats:italic>‐acetyl cysteine completely blocked the inductions of HBD‐3 and IL‐8 and significantly reduced HBD‐2 induction by <jats:italic>F. nucleatum</jats:italic>, confirming the importance of ROS in the host response. In sum, <jats:italic>T. denticola</jats:italic> incapacitates the <jats:italic>F. nucleatum</jats:italic>‐induced expression of HBDs and IL‐8 in gingival epithelial cells by interrupting endo‐lysosomal maturation and ROS‐dependent TLR activation. These results may provide new insights into polymicrobial interactions in the gingival sulcus.</jats:p>","journal":"Immunology &amp; Cell Biology","year":2013,"id":645623,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1681201,"name":"Keum Jin Baek","orcid":null,"position":1,"is_corresponding":false},{"id":1681202,"name":"Yun Sik Choi","orcid":null,"position":2,"is_corresponding":false},{"id":1681203,"name":"Youngnim Choi","orcid":null,"position":3,"is_corresponding":false},{"id":1681200,"name":"Ji Eun Shin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A periodontal pathogen <i>Treponema denticola</i> hijacks the <i>Fusobacterium nucleatum</i>‐driven host response","abstract":"<jats:p>Periodontitis is a polymicrobial disease that arises from the dysbiosis of the plaque biofilm. To study polymicrobial interactions with gingival epithelial cells, the oral commensal <jats:italic>Fusobacterium nucleatum</jats:italic> and the periodontal pathogen <jats:italic>Treponema denticola</jats:italic> were chosen due to their opposing effects on the expression of human beta‐defensins (HBDs) and interleukin (IL)‐8 in gingival epithelial cells. Immortalized gingival epithelial HOK‐16B cells were infected with either <jats:italic>F. nucleatum</jats:italic> or <jats:italic>T. denticola</jats:italic> alone or together, and the expression of HBDs and IL‐8 was investigated. Coinfection with <jats:italic>F. nucleatum</jats:italic> and <jats:italic>T. denticola</jats:italic> neutralized the stimulatory and suppressive effects on the expression of HBD‐2 and ‐3, but the suppressive effect of <jats:italic>T. denticola</jats:italic> on IL‐8 expression remained. In CHO/CD14/TLR2 reporter cells, <jats:italic>T. denticola</jats:italic> attenuated <jats:italic>F. nucleatum</jats:italic>‐induced activation of TLR2, a receptor that mediates HBD induction. Although <jats:italic>F. nucleatum</jats:italic> facilitated the invasion of <jats:italic>T. denticola</jats:italic> into host cells, <jats:italic>T. denticola</jats:italic> interfered with the fusion of internalized <jats:italic>F. nucleatum</jats:italic> with lysosomes, which may avert TLR9‐dependent IL‐8 induction. Furthermore, <jats:italic>T. denticola</jats:italic> suppressed the <jats:italic>F. nucleatum</jats:italic>‐stimulated accumulation of intracellular reactive oxygen species (ROS), a group of essential signaling molecules for the TLR2 and TLR9 pathways. The elimination of ROS using <jats:italic>N</jats:italic>‐acetyl cysteine completely blocked the inductions of HBD‐3 and IL‐8 and significantly reduced HBD‐2 induction by <jats:italic>F. nucleatum</jats:italic>, confirming the importance of ROS in the host response. In sum, <jats:italic>T. denticola</jats:italic> incapacitates the <jats:italic>F. nucleatum</jats:italic>‐induced expression of HBDs and IL‐8 in gingival epithelial cells by interrupting endo‐lysosomal maturation and ROS‐dependent TLR activation. These results may provide new insights into polymicrobial interactions in the gingival sulcus.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23897119","pmcid":null,"openalex_id":"https://openalex.org/W2093453283","authors":[],"funders":[],"total_grants":0,"fwci":2.2916,"citation_percentile":0.87175951,"influential_citations":0,"citation_trend":[{"year":2014,"count":5},{"year":2015,"count":2},{"year":2016,"count":2},{"year":2017,"count":4},{"year":2018,"count":2},{"year":2022,"count":3},{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Ficb.2013.35","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1038/icb.2013.35","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1038/icb.2013.35","host_type":"publisher"},{"url":"https://doi.org/10.1038/icb.2013.35","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23897119","host_type":"repository"},{"url":"https://hdl.handle.net/10371/190713","host_type":"repository"}],"fields_of_study":["Oral microbiology and periodontitis research","Oral Health Pathology and Treatment","HIV/AIDS oral health manifestations"],"mesh_terms":["Animals","Cricetulus","Epithelial Cells","Gingiva","Humans","Membrane Fusion","Periodontitis","Endosomes","CHO Cells","Fusobacterium nucleatum","Reactive Oxygen Species","Transgenes","beta-Defensins","Treponema denticola","Toll-Like Receptor 2","Host-Pathogen Interactions","Coinfection","Microbiota"],"keywords":["Treponema denticola","Fusobacterium nucleatum","Host (biology)","Periodontal pathogen","Pathogen","Biology","Treponema","Microbiology","Host response","Periodontal disease","Virology","Medicine","Immunology","Bacteria","Porphyromonas gingivalis","Immune system","Dentistry","Ecology","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T09:34:49.396941Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}