{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:43:06Z","timestamp":1780504986082,"version":"3.54.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Fusobacterium necrophorum<\/jats:italic> can cause liver abscess, foot rot in ruminants, and Lemire syndrome in humans, Also, its virulence factors can induce the apoptosis of macrophages and neutrophils. However, the detailed mechanism has not been fully clarified. This study investigated the mechanisms of apoptosis and inflammatory factor production in <jats:italic>F. necrophorum<\/jats:italic>\u2013induced neutrophils and macrophages (RAW246.7). After infection of macrophages with <jats:italic>F. necrophorum<\/jats:italic>, 5-ethynyl-2\u2019-deoxyuridine labeling assays indicated that <jats:italic>F. necrophorum<\/jats:italic> inhibited macrophage proliferation in a time- and dose-dependent manner. Hoechst staining and DNA ladder assays showed significant condensation of the nucleus and fragmentation of genomic DNA in <jats:italic>F. necrophorum<\/jats:italic>\u2013infected macrophages, Annexin V (FITC) and propidium iodide (PI) assay confirmed the emergence of apoptosis in the macrophages and sheep neutrophils with <jats:italic>F. necrophorum<\/jats:italic> compared with the control. The group with significant apoptosis was subjected to RNA sequencing (RNA-Seq), and the sequencing results revealed 2581 up\u2013 and 2907 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed genes showed that <jats:italic>F. necrophorum<\/jats:italic> drove apoptosis and production of inflammatory factors by activating genes related to the Nuclear Factor-\u03baB (NF-\u03baB) and death receptor pathways. Meanwhile, quantitative reverse transcription PCR and Western blot validation results were consistent with the results of transcriptome sequencing analysis. In conclusion, <jats:italic>F. necrophorum<\/jats:italic> induced apoptosis and production of pro-inflammatory factors through the NF-\u03baB and death receptor signaling pathway, providing a theoretical basis for further mechanistic studies on the prevention and control of <jats:italic>F. necrophorum<\/jats:italic> disease treatment.<\/jats:p>","DOI":"10.3389\/fcimb.2022.827750","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T07:16:31Z","timestamp":1655190991000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Fusobacterium necrophorum Promotes Apoptosis and Inflammatory Cytokine Production Through the Activation of NF-\u03baB and Death Receptor Signaling Pathways"],"prefix":"10.3389","volume":"12","author":[{"given":"Feng-Feng","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Jing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Shuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Bo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hua","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/jas\/skaa359","article-title":"Rumen Epithelial Transcriptome and Microbiome Profiles of Rumen Epithelium and Contents of Beef Cattle With and Without Liver Abscesses","volume":"98","author":"Abbas","year":"2020","journal-title":"J. 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