{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:34:26Z","timestamp":1785540866211,"version":"3.56.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M011186\/1, BB\/K009443\/1"],"award-info":[{"award-number":["BB\/M011186\/1, BB\/K009443\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Bovine digital dermatitis (BDD) is a common infectious disease of digital skin in cattle and an important cause of lameness worldwide, with limited treatment options. It is of increasing global concern for both animal welfare and food security, imposing a large economic burden on cattle farming industries each year. A polytreponemal etiology has been consistently identified, with three key phylogroups implicated globally:<jats:italic>Treponema medium, Treponema phagedenis<\/jats:italic>, and<jats:italic>Treponema pedis.<\/jats:italic>Pathogenic mechanisms which might enable targeted treatment\/therapeutic development are poorly defined. This study used RNA sequencing to determine global differential mRNA expression in primary bovine foot skin fibroblasts following challenge with three representative BDD treponemes and a commensal treponeme,<jats:italic>Treponema ruminis<\/jats:italic>. A pro-inflammatory response was elicited by the BDD treponemes, mediated through<jats:italic>IL-8\/IL-17<\/jats:italic>signaling. Unexpectedly, the three BDD treponemes elicited distinct mechanisms of pathogenesis.<jats:italic>T. phagedenis<\/jats:italic>and<jats:italic>T. pedis<\/jats:italic>increased abundance of mRNA transcripts associated with apoptosis, while<jats:italic>T. medium<\/jats:italic>and<jats:italic>T. pedis<\/jats:italic>increased transcripts involved in actin rearrangement and loss of cell adhesion, likely promoting tissue invasion. The upregulation of antimicrobial peptide precursor, DEFB123, by<jats:italic>T. phagedenis<\/jats:italic>spirochaetes may present a microbial ecological advantage to all treponemes within BDD infected tissue, explaining their dominance within lesions. A commensal,<jats:italic>T. ruminis<\/jats:italic>, significantly dysregulated over three times the number of host mRNA transcripts compared to BDD treponemes, implying BDD treponemes, akin to the syphilis pathogen (<jats:italic>Treponema pallidum<\/jats:italic>), have evolved as \u201cstealth pathogens\u201d which avoid triggering substantial host immune\/inflammatory responses to enable persistence and tissue invasion. Immunohistochemistry demonstrated increased IL-6, IL-8, RND1, and CFB protein expression in BDD lesions, confirming<jats:italic>in vitro<\/jats:italic>fibroblast observations and highlighting the system\u2019s value in modeling BDD pathogenesis. Several unique shared gene targets were identified, particularly<jats:italic>RGS16<\/jats:italic>,<jats:italic>GRO1<\/jats:italic>,<jats:italic>MAFF<\/jats:italic>, and<jats:italic>ZC3H12A<\/jats:italic>. The three key BDD<jats:italic>Treponema<\/jats:italic>phylogroups elicited both distinct and shared pathogenic mechanisms in bovine foot skin; upregulating inflammation whilst simultaneously suppressing adaptive immunity. The novel gene targets identified here should enable future vaccine\/therapeutic approaches.<\/jats:p>","DOI":"10.3389\/fcimb.2020.538591","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T12:13:38Z","timestamp":1610108018000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Challenge of Bovine Foot Skin Fibroblasts With Digital Dermatitis Treponemes Identifies Distinct Pathogenic Mechanisms"],"prefix":"10.3389","volume":"10","author":[{"given":"Kerry","family":"Newbrook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart D.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Crosby-Durrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"W3","DOI":"10.1093\/nar\/gkw343","article-title":"The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update","volume":"44","author":"Afgan","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw1104","article-title":"Ensembl 2017","author":"Aken","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1006\/excr.2002.5576","article-title":"The WASP-binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor","volume":"279","author":"Aspenstr\u00f6m","year":"2002","journal-title":"Exp. Cell Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1182\/blood.V98.3.743","article-title":"Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kB","volume":"98","author":"Ayroldi","year":"2001","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1128\/IAI.60.8.3360-3368.1992","article-title":"Treponema denticola induces actin rearrangement and detachment of human gingival fibroblasts","volume":"60","author":"Baehni","year":"1992","journal-title":"Infect. Immun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1182\/blood-2002-02-0538","article-title":"Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10","volume":"101","author":"Berrebi","year":"2003","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"555","DOI":"10.2460\/javma.237.5.555","article-title":"Clinical, histologic, and bacteriologic findings in dairy cows with digital dermatitis (footwarts) one month after topical treatment with lincomycin hydrochloride or oxytetracycline hydrochloride","volume":"237","author":"Berry","year":"2010","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4586","DOI":"10.3168\/jds.2007-0297","article-title":"Visual locomotion scoring in the first seventy days in milk: impact on pregnancy and survival","volume":"90","author":"Bicalho","year":"2007","journal-title":"J. Dairy Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1136\/vr.122.21.505","article-title":"Digital dermatitis in dairy cattle","volume":"122","author":"Blowey","year":"1988","journal-title":"Vet. Rec."},{"key":"B10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1128\/IAI.45.1.155-159.1984","article-title":"Suppression of fibroblast proliferation by oral spirochetes","volume":"45","author":"Boehringer","year":"1984","journal-title":"Infect. Immun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/j.1399-302x.2004.00177.x","article-title":"Resistance to human beta-defensins is common among oral treponemes","volume":"19","author":"Brissette","year":"2004","journal-title":"Oral. Microbiol. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1017\/S1751731111002606","article-title":"Assessing the welfare impact of foot disorders in dairy cattle by a modelling approach","volume":"6","author":"Bruijnis","year":"2012","journal-title":"Animal"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3437","DOI":"10.1128\/IAI.71.6.3437-3442.2003","article-title":"Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi","volume":"71","author":"Burchill","year":"2003","journal-title":"Infect. Immun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S0165-2427(99)00007-0","article-title":"Production and functional characterization of recombinant bovine interleukin-8 as a specific neutrophil activator and chemoattractant","volume":"67","author":"Caswell","year":"1999","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.jcpa.2016.04.001","article-title":"Severe foot lesions in dairy goats associated with digital dermatitis treponemes","volume":"154","author":"Crosby-Durrani","year":"2016","journal-title":"J. Comp. Pathol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1717","DOI":"10.1371\/journal.pntd.0001717","article-title":"Immune evasion and recognition of the syphilis spirochete in blood\u00a0and skin of secondary syphilis patients: two immunologically distinct compartments","volume":"6","author":"Cruz","year":"2012","journal-title":"PloS Negl. Trop. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1136\/vr.140.24.620","article-title":"Histological and bacteriological evaluation of digital dermatitis in cattle, with special reference to spirochaetes and Campylobacter faecalis","volume":"140","author":"D\u00f6pfer","year":"1997","journal-title":"Vet. Rec."},{"key":"B18","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.4049\/jimmunol.158.7.3285","article-title":"Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts","volume":"158","author":"Ebnet","year":"1997","journal-title":"J. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.jaci.2006.08.027","article-title":"The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells","volume":"119","author":"Eddleston","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.vetmic.2007.12.019","article-title":"Three unique groups of spirochetes isolated from digital dermatitis lesions in UK cattle","volume":"130","author":"Evans","year":"2008","journal-title":"Vet. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1128\/JCM.01914-08","article-title":"Association of unique, isolated treponemes with bovine digital dermatitis lesions","volume":"47","author":"Evans","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1099\/ijs.0.002287-0","article-title":"Treponema pedis sp. nov., a spirochaete isolated from bovine digital dermatitis lesions","volume":"59","author":"Evans","year":"2009","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1128\/AEM.00993-10","article-title":"Characterization of novel bovine gastrointestinal tract Treponema isolates and comparison with bovine digital dermatitis treponemes","volume":"77","author":"Evans","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.vetimm.2014.05.005","article-title":"Differential inflammatory responses of bovine foot skin fibroblasts and keratinocytes to digital dermatitis treponemes","volume":"161","author":"Evans","year":"2014","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"5315","DOI":"10.1093\/emboj\/19.20.5315","article-title":"In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin","volume":"19","author":"Fullner","year":"2000","journal-title":"EMBO J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.immuni.2015.07.021","article-title":"MCPIP1 endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation","volume":"43","author":"Garg","year":"2015","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1091\/mbc.9.6.1379","article-title":"RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs","volume":"9","author":"Gauthier-Rouvi\u00e9re","year":"1998","journal-title":"Mol. Biol. Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.3168\/jds.2011-4754","article-title":"An experimental infection model to induce digital dermatitis infection in cattle","volume":"95","author":"Gomez","year":"2012","journal-title":"J. Dairy Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4487","DOI":"10.3168\/jds.2014-9041","article-title":"First-lactation performance in cows affected by digital dermatitis during the rearing period","volume":"98","author":"Gomez","year":"2015","journal-title":"J. Dairy Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.3168\/jds.S0022-0302(02)74304-X","article-title":"The impact of clinical lameness on the milk yield of dairy cows","volume":"85","author":"Green","year":"2002","journal-title":"J. Dairy Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4876","DOI":"10.1128\/IAI.05451-11","article-title":"Interleukin-10 alters effector functions of multiple genes induced by Borrelia burgdorferi in macrophages to regulate Lyme disease inflammation","volume":"79","author":"Guatam","year":"2011","journal-title":"Infect. Immun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"5332","DOI":"10.1093\/emboj\/20.19.5332","article-title":"IL-17s adopt a cysteine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding","volume":"20","author":"Hymowitz","year":"2001","journal-title":"EMBO J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6107","DOI":"10.4049\/jimmunol.165.11.6107","article-title":"Microbial lipopeptides induce the production of IL-17 in Th cells","volume":"165","author":"Infante-Duarte","year":"2000","journal-title":"J. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.immuni.2008.11.009","article-title":"Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses","volume":"30","author":"Ishigame","year":"2009","journal-title":"Immunity"},{"key":"B36","doi-asserted-by":"publisher","first-page":"16023","DOI":"10.1074\/jbc.275.21.16023","article-title":"Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages","volume":"275","author":"Ishii","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B37","unstructured":"Innate immunity: the complement system and innate immunity. The immune system in health and disease JanewayC. A. TraversP. WalportM. ShlomchikM. J. New YorkGarland ScienceImmunobiology2001"},{"key":"B38","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol."},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bar030","article-title":"Ensembl BioMarts: a hub for data retrieval across taxonomic space","author":"Kinsella","year":"2011","journal-title":"Database"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1128\/JCM.00320-13","article-title":"Targeting the treponemal microbiome of digital dermatitis infections by high-resolution phylogenetic analyses and comparison with fluorescent in situ hybridization","volume":"51","author":"Klitgaard","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"B41","first-page":"906","article-title":"Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like synovial cells","volume":"29","author":"Koga","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.jaci.2012.04.024","article-title":"IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis","volume":"130","author":"Krueger","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1056\/NEJMoa1109997","article-title":"Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis","volume":"366","author":"Leonardi","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e235","DOI":"10.1016\/j.jaad.2013.06.030","article-title":"Differential gene expression in peripheral blood T cells from patients with psoriasis, lichen planus, and atopic dermatitis","volume":"69","author":"Li","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.4049\/jimmunol.171.3.1542","article-title":"Role of regulator of G protein signaling 16 in inflammation-induced T lymphocyte migration and activation","volume":"171","author":"Lippert","year":"2003","journal-title":"J. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.tvjl.2012.06.050","article-title":"A field evaluation of a footbathing solution for the control of digital dermatitis in cattle","volume":"193","author":"Logue","year":"2012","journal-title":"Vet. J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1017\/S0022029906001798","article-title":"Economic impacts of reduced milk production associated with papillomatous digital dermatitis in dairy cows in the USA","volume":"73","author":"Losinger","year":"2006","journal-title":"J. Dairy Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3007.1","DOI":"10.1186\/gb-2002-3-5-reviews3007","article-title":"The ADF\/cofilin family: actin-remodeling proteins","volume":"3","author":"Maciver","year":"2002","journal-title":"Genome Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1038\/jid.2009.73","article-title":"Defensin is suppressed by tick salivary gland extract during the in vitro interaction of resident skin cells with Borrelia burgdorferi","volume":"129","author":"Marchal","year":"2009","journal-title":"J. Invest. Dermatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet.journal"},{"key":"B51","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1095\/biolreprod.105.045450","article-title":"Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells","volume":"74","author":"Massrieh","year":"2006","journal-title":"Biol. Reprod."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e0164117","DOI":"10.1371\/journal.pone.0164117","article-title":"Homogeneous inflammatory gene profiles induced in human dermal fibroblasts in response to the three main species of Borrelia burgdorferi sensu lato","volume":"11","author":"Meddeb","year":"2016","journal-title":"PloS One"},{"key":"B53","doi-asserted-by":"publisher","first-page":"29603","DOI":"10.1074\/jbc.M101522200","article-title":"Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ","volume":"276","author":"Mittelstadt","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B54","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.molmed.2004.09.003","article-title":"Nrf2-Keap1 defines a physiologically important stress response mechanism","volume":"10","author":"Motohashi","year":"2004","journal-title":"Trends Mol. Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1099\/ijsem.0.001812","article-title":"Treponema ruminis sp. nov., a spirochaete isolated from the bovine rumen","volume":"67","author":"Newbrook","year":"2017","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"B56","volume-title":"Dissecting host-pathogen interactions in bovine digital dermatitis [PhD thesis]","author":"Newbrook","year":"2017"},{"key":"B57","doi-asserted-by":"publisher","first-page":"5284","DOI":"10.1128\/IAI.68.9.5284-5292.2000","article-title":"Cytokine responses to Treponema pectinovorum and Treponema denticola in human gingival fibroblasts","volume":"68","author":"Nixon","year":"2000","journal-title":"Infect. Immun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1083\/jcb.141.1.187","article-title":"A new member of the Rho family, Rnd1, promotes disassembly of actin filament structures and loss of cell adhesion","volume":"141","author":"Nobes","year":"1998","journal-title":"J. Cell Biol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/978-1-4684-1248-2_65","article-title":"On the role of cytidine deaminase in cellular metabolism","volume":"195","author":"Nygaard","year":"1986","journal-title":"Adv. Exp. Med. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/nrmicro.2016.141","article-title":"Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen","volume":"14","author":"Radolf","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.3168\/jds.2014-8863","article-title":"Low body condition predisposes cattle to lameness: an 8-year study of one dairy herd","volume":"98","author":"Randall","year":"2015","journal-title":"J. Dairy Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1186\/1746-6148-9-193","article-title":"Digital dermatitis in cattle is associated with an excessive innate immune response triggered by the keratinocytes","volume":"9","author":"Refaai","year":"2013","journal-title":"BMC Vet. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.3168\/jds.2012-5934","article-title":"Association between digital dermatitis lesions and test-day milk yield of Holstein cows from 41 French dairy farms","volume":"96","author":"Relun","year":"2013","journal-title":"J. Dairy Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1016\/j.jid.2016.04.030","article-title":"MCPIP1 RNase is aberrantly distributed in psoriatic epidermis and rapidly induced by IL-17a","volume":"136","author":"Ruiz-Romeu","year":"2016","journal-title":"J. Invest. Dermatol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/mmi.12377","article-title":"Borrelia burgdorferi BbHtrA degrades host ECM proteins and stimulates release of inflammatory cytokines in vitro","volume":"90","author":"Russell","year":"2013","journal-title":"Mol. Microbiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.tvjl.2013.03.008","article-title":"Identifying the host pathogenic pathways in bovine digital dermatitis by RNA-Seq analysis","volume":"197","author":"Scholey","year":"2013","journal-title":"Vet. J."},{"key":"B68","doi-asserted-by":"publisher","first-page":"e40046","DOI":"10.1371\/journal.pone.0040046","article-title":"Microarray analyses of inflammation response of human dermal fibroblasts to different strains of Borrelia burgdorferi sensu stricto","volume":"7","author":"Schramm","year":"2012","journal-title":"PloS One"},{"key":"B69","doi-asserted-by":"publisher","first-page":"6347","DOI":"10.4049\/jimmunol.1103781","article-title":"RGS16 attenuates pulmonary Th2\/Th17 inflammatory responses","volume":"188","author":"Shankar","year":"2012","journal-title":"J. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1034\/j.1600-0722.2000.90771.x","article-title":"Superoxide release and superoxide dismutase expression by human gingival fibroblasts","volume":"108","author":"Skaleri\u010d","year":"2000","journal-title":"Eur. J. Oral. Sci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1089\/jir.2009.0033","article-title":"Gram-positive and Gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness","volume":"30","author":"Skovbjerg","year":"2010","journal-title":"J. Interferon Cytokine Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.1128\/JCM.40.9.3463-3469.2002","article-title":"Molecular typing of papillomatous digital dermatitis-associated Treponema isolates based on analysis of 16S-23S ribosomal DNA intergenic spacer regions","volume":"40","author":"Stamm","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/bioinformatics\/18.1.207","article-title":"Genesis: cluster analysis of microarray data","volume":"18","author":"Sturn","year":"2002","journal-title":"Bioinformatics"},{"key":"B74","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1136\/vr.101802","article-title":"Digital dermatitis in beef cattle","volume":"173","author":"Sullivan","year":"2013","journal-title":"Vet. Rec."},{"key":"B75","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/sji.12250","article-title":"RGS16 restricts the pro-inflammatory response of monocytes","volume":"81","author":"Suurv\u00e4li","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1242\/jcs.098087","article-title":"Actin stress fibers \u2013 assembly, dynamics and biological roles","volume":"125","author":"Tojkander","year":"2012","journal-title":"J. Cell Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-Seq experiments with TopHat and Cufflinks","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat. Protoc."},{"key":"B79","doi-asserted-by":"publisher","first-page":"e23736","DOI":"10.1371\/journal.pone.0023736","article-title":"Treponema denticola major outer sheath protein induces actin assembly at free barbed ends by a PIP2-dependent uncapping mechanism in fibroblasts","volume":"6","author":"Visser","year":"2011","journal-title":"PloS One"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.bbrc.2005.03.082","article-title":"NELIN, a new F-actin associated protein, stimulates HeLa cell migration and adhesion","volume":"330","author":"Wang","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B81","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1128\/IAI.66.2.696-702.1998","article-title":"Filamentous actin disruption and diminished inositol phosphate response in gingival fibroblasts caused by Treponema denticola","volume":"66","author":"Yang","year":"1998","journal-title":"Infect. Immun."},{"key":"B82","doi-asserted-by":"publisher","first-page":"R42","DOI":"10.1186\/gb-2009-10-4-r42","article-title":"A whole-genome assembly of the domestic cow, Bos taurus","volume":"10","author":"Zimin","year":"2009","journal-title":"Genome Biol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"e0133674","DOI":"10.1371\/journal.pone.0133674","article-title":"Shotgun metagenomic sequencing reveals functional genes and microbiome associated with bovine digital dermatitis","volume":"10","author":"Zinicola","year":"2015","journal-title":"PloS One"},{"key":"B84","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.vetmic.2007.06.001","article-title":"Papillomatous digital dermatitis spirochetes suppress the bovine macrophage innate immune response","volume":"125","author":"Zuerner","year":"2007","journal-title":"Vet. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.538591\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T06:37:55Z","timestamp":1697524675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.538591\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":84,"alternative-id":["10.3389\/fcimb.2020.538591"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2020.538591","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"article-number":"538591"}}