{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:11:12Z","timestamp":1777399872530,"version":"3.51.4"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["AGL2016- 75202-R"],"award-info":[{"award-number":["AGL2016- 75202-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["Ref. AGL2013-04442"],"award-info":[{"award-number":["Ref. AGL2013-04442"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["Ref. P2018\/BAA-4370"],"award-info":[{"award-number":["Ref. P2018\/BAA-4370"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Bovine besnoitiosis, caused by the cyst-forming apicomplexan parasite <jats:italic>Besnoitia besnoiti<\/jats:italic>, is a chronic and debilitating cattle disease that continues to spread in Europe in the absence of control tools. In this scenario, <jats:italic>in vitro<\/jats:italic> culture systems are valuable tools to carry out drug screenings and to unravel host-parasite interactions. However, studies performed in bovine target cells are scarce.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The objective of the present study was to obtain primary bovine aortic endothelial cells (BAECs) and fibroblast cell cultures, target cells during the acute and the chronic stage of the disease, respectively, from healthy bovine donors. Afterwards, expression of surface (CD31, CD34 and CD44) and intracellular markers (vimentin and cytokeratin) was studied to characterize cell populations by flow cytometry. Next, the lytic cycle of <jats:italic>B. besnoiti<\/jats:italic> tachyzoites was studied in both target cells. Invasion rates (IRs) were determined by immunofluorescence at several time points post-infection, and proliferation kinetics were studied by quantitative PCR (qPCR). Finally, the influence of bovine viral diarrhea virus (BVDV) co-infection on the host cell machinery, and consequently on <jats:italic>B. besnoiti<\/jats:italic> invasion and proliferation, was investigated in BAECs.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Morphology and cytometry results confirmed the endothelial and fibroblast origins. CD31 was the surface marker that best discriminated between BAECs and fibroblasts, since fibroblasts lacked CD31 labelling. Expression of CD34 was weak in low-passage BAECs and absent in high-passage BAECs and fibroblasts. Positive labelling for CD44, vimentin and cytokeratin was observed in both BAECs and fibroblasts. Regarding the lytic cycle of the parasite, although low invasion rates (approximately 3\u20134%) were found in both cell culture systems, more invasion was observed in BAECs at 24 and 72 hpi. The proliferation kinetics did not differ between BAECs and fibroblasts. BVDV infection favoured early <jats:italic>Besnoitia<\/jats:italic> invasion but there was no difference in tachyzoite yields observed in BVDV-BAECs compared to BAECs.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We have generated and characterized two novel standardized <jats:italic>in vitro<\/jats:italic> models for <jats:italic>Besnoitia besnoiti<\/jats:italic> infection based on bovine primary target BAECs and fibroblasts, and have shown the relevance of BVDV coinfections, which should be considered in further studies with other cattle pathogens.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13071-019-3777-0","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T13:03:24Z","timestamp":1572872604000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lytic cycle of Besnoitia besnoiti tachyzoites displays similar features in primary bovine endothelial cells and fibroblasts"],"prefix":"10.1186","volume":"12","author":[{"given":"Alejandro","family":"Jim\u00e9nez-Mel\u00e9ndez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Fern\u00e1ndez-\u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Calle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel \u00c1ngel","family":"Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Diezma-D\u00edaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"V\u00e1zquez-Arbaizar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Miguel","family":"Ortega-Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gema","family":"\u00c1lvarez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"3777_CR1","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1017\/S0031182014000729","volume":"141","author":"G \u00c1lvarez-Garc\u00eda","year":"2014","unstructured":"\u00c1lvarez-Garc\u00eda G, Garc\u00eda-Lunar P, Guti\u00e9rrez-Exp\u00f3sito D, Shkap V, Ortega-Mora LM. Dynamics of Besnoitia besnoiti infection in cattle. Parasitology. 2014;141:1419\u201335.","journal-title":"Parasitology."},{"key":"3777_CR2","first-page":"265","volume":"28","author":"JW Pols","year":"1960","unstructured":"Pols JW. Studies on bovine besnoitiosis with special reference to the aetiology. Onderstepoort J Vet Res. 1960;28:265\u2013356.","journal-title":"Onderstepoort J Vet Res."},{"key":"3777_CR3","first-page":"105","volume":"37","author":"P Basson","year":"1970","unstructured":"Basson P, McCully R, Bigalke R. Observations on the pathogenesis of bovine and antelope strains of Besnoitia besnoiti (Marotel, 1912) infection in cattle and rabbits. Onderstepoort J Vet Res. 1970;37:105\u201326.","journal-title":"Onderstepoort J Vet Res."},{"key":"3777_CR4","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1177\/0300985814541705","volume":"52","author":"MC Langenmayer","year":"2015","unstructured":"Langenmayer MC, Gollnick NS, Majzoub-Altweck M, Scharr JC, Schares G, Hermanns W. Naturally acquired bovine besnoitiosis: histological and immunohistochemical findings in acute, subacute, and chronic disease. Vet Pathol. 2015;52:476\u201388.","journal-title":"Vet Pathol."},{"key":"3777_CR5","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1645\/12-128.1","volume":"99","author":"JP Dubey","year":"2013","unstructured":"Dubey JP, van Wilpe E, Blignaut DJ, Schares G, Williams JH. Development of early tissue cysts and associated pathology of Besnoitia besnoiti in a naturally infected bull (Bos taurus) from South Africa. J Parasitol. 2013;99:459\u201366.","journal-title":"J Parasitol."},{"key":"3777_CR6","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.ijpara.2017.08.003","volume":"47","author":"D Guti\u00e9rrez-Exp\u00f3sito","year":"2017","unstructured":"Guti\u00e9rrez-Exp\u00f3sito D, Ferre I, Ortega-Mora LM, \u00c1lvarez-Garc\u00eda G. Advances in the diagnosis of bovine besnoitiosis: current options and applications for control. Int J Parasitol. 2017;47:737\u201351.","journal-title":"Int J Parasitol."},{"key":"3777_CR7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ijpara.2012.08.004","volume":"43","author":"J M\u00fcller","year":"2013","unstructured":"M\u00fcller J, Hemphill A. In vitro culture systems for the study of apicomplexan parasites in farm animals. Int J Parasitol. 2013;43:115\u201324.","journal-title":"Int J Parasitol."},{"key":"3777_CR8","first-page":"243","volume":"25","author":"M Neuman","year":"1974","unstructured":"Neuman M. Cultivation of Besnoitia besnoiti Marotel, 1912, in cell culture. Tropenmed Parasitol. 1974;25:243\u20139.","journal-title":"Tropenmed Parasitol."},{"key":"3777_CR9","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/0020-7519(88)90136-1","volume":"18","author":"M Samish","year":"1988","unstructured":"Samish M, Shkap V, Bin H, Pipano EM. Cultivation of Besnoitia besnoiti in four tick cell lines. Int J Parasitol. 1988;18:291\u20136.","journal-title":"Int J Parasitol."},{"key":"3777_CR10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.vetpar.2009.04.033","volume":"163","author":"G Schares","year":"2009","unstructured":"Schares G, Basso W, Majzoub M, Cortes HC, Rostaher A, Selmair J, et al. First in vitro isolation of Besnoitia besnoiti from chronically infected cattle in Germany. Vet Parasitol. 2009;163:315\u201322.","journal-title":"Vet Parasitol."},{"key":"3777_CR11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s13071-016-1405-9","volume":"9","author":"CF Frey","year":"2016","unstructured":"Frey CF, Regidor-Cerrillo J, Marreros N, Garc\u00eda-Lunar P, Guti\u00e9rrez-Exp\u00f3sito D, Schares G, et al. Besnoitia besnoiti lytic cycle in vitro and differences in invasion and intracellular proliferation among isolates. Parasit Vectors. 2016;9:115.","journal-title":"Parasit Vectors."},{"key":"3777_CR12","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1074\/mcp.M800258-MCP200","volume":"8","author":"C Pan","year":"2009","unstructured":"Pan C, Kumar C, Bohl S, Klingmueller U, Mann M. Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions. Mol Cell Proteomics. 2009;8:443\u201350.","journal-title":"Mol Cell Proteomics."},{"key":"3777_CR13","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1007\/s00436-016-4941-5","volume":"115","author":"P Maksimov","year":"2016","unstructured":"Maksimov P, Hermosilla C, Kleinertz S, Hirzmann J, Taubert A. Besnoitia besnoiti infections activate primary bovine endothelial cells and promote PMN adhesion and NET formation under physiological flow condition. Parasitol Res. 2016;115:1991\u20132001.","journal-title":"Parasitol Res."},{"key":"3777_CR14","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1007\/s00436-016-4946-0","volume":"115","author":"A Taubert","year":"2016","unstructured":"Taubert A, Hermosilla C, Silva L, Wieck A, Failing K, Mazurek S. Metabolic signatures of Besnoitia besnoiti-infected endothelial host cells and blockage of key metabolic pathways indicate high glycolytic and glutaminolytic needs of the parasite. Parasitol Res. 2016;115:2023\u201334.","journal-title":"Parasitol Res."},{"key":"3777_CR15","doi-asserted-by":"publisher","first-page":"4189","DOI":"10.1007\/s00436-014-4094-3","volume":"113","author":"T Mu\u00f1oz-Caro","year":"2014","unstructured":"Mu\u00f1oz-Caro T, Silva LM, Ritter C, Taubert A, Hermosilla C. Besnoitia besnoiti tachyzoites induce monocyte extracellular trap formation. Parasitol Res. 2014;113:4189\u201397.","journal-title":"Parasitol Res."},{"key":"3777_CR16","doi-asserted-by":"publisher","first-page":"e91415","DOI":"10.1371\/journal.pone.0091415","volume":"9","author":"T Mu\u00f1oz-Caro","year":"2014","unstructured":"Mu\u00f1oz-Caro T, Hermosilla C, Silva LM, Cortes H, Taubert A. Neutrophil extracellular traps as innate immune reaction against the emerging apicomplexan parasite Besnoitia besnoiti. PloS One. 2014;9:e91415.","journal-title":"PloS One."},{"key":"3777_CR17","doi-asserted-by":"publisher","first-page":"a006429","DOI":"10.1101\/cshperspect.a006429","volume":"2","author":"WC Aird","year":"2012","unstructured":"Aird WC. Endothelial cell heterogeneity. Cold Spring Harbor perspectives in medicine. 2012;2:a006429.","journal-title":"Cold Spring Harbor perspectives in medicine."},{"key":"3777_CR18","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13567-017-0499-1","volume":"49","author":"N B\u00fcrgi","year":"2018","unstructured":"B\u00fcrgi N, Josi C, B\u00fcrki S, Schweizer M, Pilo P. Mycoplasma bovis co-infection with bovine viral diarrhea virus in bovine macrophages. Vet Res. 2018;49:2.","journal-title":"Vet Res."},{"key":"3777_CR19","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.biologicals.2014.02.002","volume":"42","author":"L Gagnieur","year":"2014","unstructured":"Gagnieur L, Cheval J, Gratigny M, H\u00e9bert C, Muth E, Dumarest M, et al. Unbiased analysis by high throughput sequencing of the viral diversity in fetal bovine serum and trypsin used in cell culture. Biologicals. 2014;42:145\u201352.","journal-title":"Biologicals."},{"key":"3777_CR20","first-page":"93","volume":"132","author":"JD Neill","year":"2008","unstructured":"Neill JD, Ridpath JF, Lange A, Zuerner RL. Bovine viral diarrhoea virus infection alters global transcription profiles in bovine endothelial cells. Dev Biol (Basel). 2008;132:93\u20138.","journal-title":"Dev Biol (Basel)."},{"key":"3777_CR21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1865-1682.2012.01318.x","volume":"60","author":"P Garc\u00eda-Lunar","year":"2013","unstructured":"Garc\u00eda-Lunar P, Ortega-Mora LM, Schares G, Gollnick NS, Jacquiet P, Grisez C, et al. An inter-laboratory comparative study of serological tools employed in the diagnosis of Besnoitia besnoiti infection in bovines. Transbound Emerg Dis. 2013;60:59\u201368.","journal-title":"Transbound Emerg Dis."},{"key":"3777_CR22","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1051\/vetres:2003009","volume":"34","author":"G \u00c1lvarez-Garc\u00eda","year":"2003","unstructured":"\u00c1lvarez-Garc\u00eda G, Collantes-Fern\u00e1ndez E, Costas E, Rebordosa X, Ortega-Mora LM. Influence of age and purpose for testing on the cut-off selection of serological methods in bovine neosporosis. Vet Res. 2003;34:341\u201352.","journal-title":"Vet Res."},{"key":"3777_CR23","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.jcyt.2014.01.010","volume":"16","author":"F Ataollahi","year":"2014","unstructured":"Ataollahi F, Pingguan-Murphy B, Moradi A, Abas WA, Chua KH, Osman NA. New method for the isolation of endothelial cells from large vessels. Cytotherapy. 2014;16:1145\u201352.","journal-title":"Cytotherapy"},{"key":"3777_CR24","volume-title":"Animal cell culture techniques","author":"F OSullivan","year":"1998","unstructured":"OSullivan F, Meleady P, McBride S, Clynes M. Primary culture. In: Clynes M, editor. Animal cell culture techniques. New York: Springer; 1998."},{"key":"3777_CR25","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.jviromet.2006.05.020","volume":"136","author":"B Hoffmann","year":"2006","unstructured":"Hoffmann B, Depner K, Schirrmeier H, Beer M. A universal heterologous internal control system for duplex real-time RT-PCR assays used in a detection system for pestiviruses. J Virol Methods. 2006;136:200\u20139.","journal-title":"J Virol Methods."},{"key":"3777_CR26","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1645\/GE-1772.1","volume":"95","author":"A Fern\u00e1ndez-Garc\u00eda","year":"2009","unstructured":"Fern\u00e1ndez-Garc\u00eda A, Risco-Castillo V, Pedraza-D\u00edaz S, Aguado-Mart\u00ednez A, \u00c1lvarez-Garc\u00eda G, G\u00f3mez-Bautista M, et al. First isolation of Besnoitia besnoiti from a chronically infected cow in Spain. J Parasitol. 2009;95:474\u20136.","journal-title":"J Parasitol."},{"key":"3777_CR27","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13287-018-1129-1","volume":"10","author":"A Calle","year":"2019","unstructured":"Calle A, L\u00f3pez-Mart\u00edn S, Mongui\u00f3-Tortajada M, Borr\u00e0s FE, Y\u00e1\u00f1ez-M\u00f3 M, Ram\u00edrez M\u00c1. Bovine endometrial MSC: mesenchymal to epithelial transition during luteolysis and tropism to implantation niche for immunomodulation. Stem Cell Res Ther. 2019;10:23.","journal-title":"Stem Cell Res Ther."},{"key":"3777_CR28","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.vetpar.2013.05.017","volume":"197","author":"D Guti\u00e9rrez-Exp\u00f3sito","year":"2013","unstructured":"Guti\u00e9rrez-Exp\u00f3sito D, Ortega-Mora LM, Marco I, Boadella M, Gortazar C, San Miguel-Ayanz JM, et al. First serosurvey of Besnoitia spp. infection in wild European ruminants in Spain. Vet Parasitol. 2013;197:557\u201364.","journal-title":"Vet Parasitol."},{"key":"3777_CR29","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.vetpar.2011.01.038","volume":"178","author":"G Schares","year":"2011","unstructured":"Schares G, Maksimov A, Basso W, Mor\u00e9 G, Dubey JP, Rosenthal B, et al. Quantitative real time polymerase chain reaction assays for the sensitive detection of Besnoitia besnoiti infection in cattle. Vet Parasitol. 2011;178:208\u201316.","journal-title":"Vet Parasitol."},{"key":"3777_CR30","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1186\/s13071-017-2409-9","volume":"10","author":"L Jim\u00e9nez-Pelayo","year":"2017","unstructured":"Jim\u00e9nez-Pelayo L, Garc\u00eda-S\u00e1nchez M, Regidor-Cerrillo J, Horcajo P, Collantes-Fern\u00e1ndez E, G\u00f3mez-Bautista M, et al. Differential susceptibility of bovine caruncular and trophoblast cell lines to infection with high and low virulence isolates of Neospora caninum. Parasit Vectors. 2017;10:463.","journal-title":"Parasit Vectors."},{"key":"3777_CR31","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s10517-012-1648-1","volume":"153","author":"L Uryvaev","year":"2012","unstructured":"Uryvaev L, Dedova A, Dedova L, Ionova K, Parasjuk N, Selivanova T, et al. Contamination of cell cultures with bovine viral diarrhea virus (BVDV). Bull Exp Biol Med. 2012;153:77\u201381.","journal-title":"Bull Exp Biol Med."},{"key":"3777_CR32","volume-title":"Biology of endothelial cells","author":"C Haudenschild","year":"1984","unstructured":"Haudenschild C. Morphology of vascular endothelial cells in culture. In: Jaffe E, editor. Biology of endothelial cells. New York: Springer; 1984."},{"key":"3777_CR33","series-title":"Wound healing: methods and protocols","volume-title":"Methods in molecular medicine","author":"P Ehrlich","year":"2003","unstructured":"Ehrlich P. The fibroblast-populated collagen. A model of fibroblast collagen interactions. In: DiPietro L, Burns AL, editors. Methods in molecular medicine, vol. 78., Wound healing: methods and protocolsNew York: Springer; 2003."},{"key":"3777_CR34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1097\/MOH.0000000000000239","volume":"23","author":"P Lertkiatmongkol","year":"2016","unstructured":"Lertkiatmongkol P, Liao D, Mei H, Hu Y, Newman PJ. Endothelial functions of platelet\/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol. 2016;23:253\u20139.","journal-title":"Curr Opin Hematol."},{"key":"3777_CR35","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1007\/s00380-017-1006-3","volume":"32","author":"DM Valencia-Nu\u00f1ez","year":"2017","unstructured":"Valencia-Nu\u00f1ez DM, Kreutler W, Moya-Gonzalez J, Alados-Arboledas P, Mu\u00f1oz-Carvajal I, Carmona A, et al. Endothelial vascular markers in coronary surgery. Heart Vessels. 2017;32:1390\u20139.","journal-title":"Heart Vessels."},{"key":"3777_CR36","doi-asserted-by":"publisher","first-page":"5357","DOI":"10.1074\/jbc.M113.529313","volume":"289","author":"M Tsuneki","year":"2014","unstructured":"Tsuneki M, Madri JA. CD44 regulation of endothelial cell proliferation and apoptosis via modulation of CD31 and VE-cadherin expression. J Biol Chem. 2014;289:5357\u201370.","journal-title":"J Biol Chem."},{"key":"3777_CR37","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/s10456-013-9346-9","volume":"16","author":"KM Flynn","year":"2013","unstructured":"Flynn KM, Michaud M, Canosa S, Madri JA. CD44 regulates vascular endothelial barrier integrity via a PECAM-1 dependent mechanism. Angiogenesis. 2013;16:689\u2013705.","journal-title":"Angiogenesis."},{"key":"3777_CR38","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1002\/jcp.25123","volume":"231","author":"M Tsuneki","year":"2016","unstructured":"Tsuneki M, Madri JA. CD44 influences fibroblast behaviors via modulation of cell-cell and cell-matrix interactions, affecting survivin and hippo pathways. J Cell Physiol. 2016;231:731\u201343.","journal-title":"J Cell Physiol."},{"key":"3777_CR39","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/S0006-3495(01)76006-7","volume":"80","author":"BP Helmke","year":"2001","unstructured":"Helmke BP, Thakker DB, Goldman RD, Davies PF. Spatiotemporal analysis of flow-induced intermediate filament displacement in living endothelial cells. Biophys J. 2001;80:184\u201394.","journal-title":"Biophys J."},{"key":"3777_CR40","doi-asserted-by":"publisher","first-page":"30814","DOI":"10.1038\/srep30814","volume":"6","author":"LC Boraas","year":"2016","unstructured":"Boraas LC, Ahsan T. Lack of vimentin impairs endothelial differentiation of embryonic stem cells. Sci Rep. 2016;6:30814.","journal-title":"Sci Rep."},{"key":"3777_CR41","doi-asserted-by":"publisher","first-page":"e01111","DOI":"10.1128\/mBio.01111-13","volume":"5","author":"KS Harker","year":"2014","unstructured":"Harker KS, Jivan E, McWhorter FY, Liu WF, Lodoen MB. Shear forces enhance Toxoplasma gondii tachyzoite motility on vascular endothelium. MBio. 2014;5:e01111\u20133.","journal-title":"MBio."},{"key":"3777_CR42","doi-asserted-by":"publisher","first-page":"E4320","DOI":"10.1073\/pnas.1519197113","volume":"113","author":"F Cheng","year":"2016","unstructured":"Cheng F, Shen Y, Mohanasundaram P, Lindstrom M, Ivaska J, Ny T, et al. Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-beta-Slug signaling. Proc Natl Acad Sci USA. 2016;113:E4320\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3777_CR43","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1046\/j.1432-0436.1994.5730225.x","volume":"57","author":"K Spanel-Borowski","year":"1994","unstructured":"Spanel-Borowski K, Ricken AM, Patton WF. Cytokeratin-positive and cytokeratin-negative cultured endothelial cells from bovine aorta and vena cava. Differentiation. 1994;57:225\u201334.","journal-title":"Differentiation."},{"key":"3777_CR44","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.mce.2011.02.021","volume":"338","author":"K Spanel-Borowski","year":"2011","unstructured":"Spanel-Borowski K. Five different phenotypes of endothelial cell cultures from the bovine corpus luteum: present outcome and role of potential dendritic cells in luteolysis. Mol Cell Endocrinol. 2011;338:38\u201345.","journal-title":"Mol Cell Endocrinol."},{"key":"3777_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0923-1811(02)00039-7","volume":"30","author":"Y Katagata","year":"2002","unstructured":"Katagata Y, Takeda H, Ishizawa T, Hozumi Y, Kondo S. Occurrence and comparison of the expressed keratins in cultured human fibroblasts, endothelial cells and their sarcomas. J Dermatol Sci. 2002;30:1\u20139.","journal-title":"J Dermatol Sci."},{"key":"3777_CR46","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.vetpar.2017.09.017","volume":"247","author":"C Diezma-D\u00edaz","year":"2017","unstructured":"Diezma-D\u00edaz C, Jim\u00e9nez-Mel\u00e9ndez A, Fern\u00e1ndez M, Guti\u00e9rrez-Exp\u00f3sito D, Garc\u00eda-Lunar P, Ortega-Mora L, et al. Bovine chronic besnoitiosis in a calf: characterization of a novel B. besnoiti isolate from an unusual case report. Vet Parasitol. 2017;247:10\u20138.","journal-title":"Vet Parasitol"},{"key":"3777_CR47","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1297-9716-42-41","volume":"42","author":"J Regidor-Cerrillo","year":"2011","unstructured":"Regidor-Cerrillo J, G\u00f3mez-Bautista M, Sodupe I, Aduriz G, \u00c1lvarez-Garc\u00eda G, Del Pozo I, et al. In vitro invasion efficiency and intracellular proliferation rate comprise virulence-related phenotypic traits of Neospora caninum. Vet Res. 2011;42:41.","journal-title":"Vet Res."},{"key":"3777_CR48","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0014-4894(03)00137-1","volume":"104","author":"A Naguleswaran","year":"2003","unstructured":"Naguleswaran A, Muller N, Hemphill A. Neospora caninum and Toxoplasma gondii: a novel adhesion\/invasion assay reveals distinct differences in tachyzoite-host cell interactions. Exp Parasitol. 2003;104:149\u201358.","journal-title":"Exp Parasitol."},{"key":"3777_CR49","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1017\/S0031182006000539","volume":"133","author":"PM Bartley","year":"2006","unstructured":"Bartley PM, Wright S, Sales J, Chianini F, Buxton D, Innes EA. Long-term passage of tachyzoites in tissue culture can attenuate virulence of Neospora caninum in vivo. Parasitology. 2006;133:421\u201332.","journal-title":"Parasitology."},{"key":"3777_CR50","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/S1286-4579(01)01425-3","volume":"3","author":"N Nischik","year":"2001","unstructured":"Nischik N, Schade B, Dytnerska K, Dlugonska H, Reichmann G, Fischer HG. Attenuation of mouse-virulent Toxoplasma gondii parasites is associated with a decrease in interleukin-12-inducing tachyzoite activity and reduced expression of actin, catalase and excretory proteins. Microb Infect. 2001;3:689\u201399.","journal-title":"Microb Infect."},{"key":"3777_CR51","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0020-7519(01)00351-4","volume":"32","author":"N Vonlaufen","year":"2002","unstructured":"Vonlaufen N, Gianinazzi C, Muller N, Simon F, Bjorkman C, Jungi TW, et al. Infection of organotypic slice cultures from rat central nervous tissue with Neospora caninum: an alternative approach to study host-parasite interactions. Int J Parasitol. 2002;32:533\u201342.","journal-title":"Int J Parasitol."},{"key":"3777_CR52","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.ijmm.2008.10.002","volume":"299","author":"Ferreira-da-Silva M da Fonseca","year":"2009","unstructured":"da Fonseca Ferreira-da-Silva M, Tak\u00e1cs AC, Barbosa HS, Gross U, L\u00fcder CG. Primary skeletal muscle cells trigger spontaneous Toxoplasma gondii tachyzoite-to-bradyzoite conversion at higher rates than fibroblasts. Int J Med Microbiol. 2009;299:381\u20138.","journal-title":"Int J Med Microbiol."},{"key":"3777_CR53","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s00436-001-0531-1","volume":"88","author":"C Hermosilla","year":"2002","unstructured":"Hermosilla C, Barbisch B, Heise A, Kowalik S, Zahner H. Development of Eimeria bovis in vitro: suitability of several bovine, human and porcine endothelial cell lines, bovine fetal gastrointestinal, Madin-Darby bovine kidney (MDBK) and African green monkey kidney (VERO) cells. Parasitol Res. 2002;88:301\u20137.","journal-title":"Parasitol Res."},{"key":"3777_CR54","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1159\/000111805","volume":"187","author":"SV Nolte","year":"2008","unstructured":"Nolte SV, Xu W, Rennekampff HO, Rodemann HP. Diversity of fibroblasts\u2014a review on implications for skin tissue engineering. Cells Tissues Organs. 2008;187:165\u201376.","journal-title":"Cells Tissues Organs."},{"key":"3777_CR55","doi-asserted-by":"publisher","first-page":"e05R01","DOI":"10.5424\/sjar\/2017152-10619","volume":"15","author":"FJ Di\u00e9guez","year":"2017","unstructured":"Di\u00e9guez FJ, Cervi\u00f1o M, Yus E. Bovine viral diarrhea virus (BVDV) genetic diversity in Spain: a review. Span J Agric Res. 2017;15:e05R01.","journal-title":"Span J Agric Res."},{"key":"3777_CR56","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S1045-1056(03)00024-1","volume":"31","author":"E Peterhans","year":"2003","unstructured":"Peterhans E, Jungi TW, Schweizer M. BVDV and innate immunity. Biologicals. 2003;31:107\u201312.","journal-title":"Biologicals."},{"key":"3777_CR57","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.biologicals.2012.09.009","volume":"41","author":"CC Chase","year":"2013","unstructured":"Chase CC. The impact of BVDV infection on adaptive immunity. Biologicals. 2013;41:52\u201360.","journal-title":"Biologicals."},{"key":"3777_CR58","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.virusres.2015.05.017","volume":"208","author":"RG Schaut","year":"2015","unstructured":"Schaut RG, McGill JL, Neill JD, Ridpath JF, Sacco RE. Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression. Virus Res. 2015;208:44\u201355.","journal-title":"Virus Res."},{"key":"3777_CR59","doi-asserted-by":"publisher","first-page":"5997","DOI":"10.4049\/jimmunol.168.12.5997","volume":"168","author":"CA Scanga","year":"2002","unstructured":"Scanga CA, Aliberti J, Jankovic D, Tilloy F, Bennouna S, Denkers EY, et al. Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells. J Immunol. 2002;168:5997\u20136001.","journal-title":"J Immunol."},{"key":"3777_CR60","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1051\/vetres\/2009015","volume":"40","author":"TW Mineo","year":"2009","unstructured":"Mineo TW, Benevides L, Silva NM, Silva JS. Myeloid differentiation factor 88 is required for resistance to Neospora caninum infection. Vet Res. 2009;40:32.","journal-title":"Vet Res."},{"key":"3777_CR61","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1053\/tvjl.1999.0446","volume":"159","author":"C Bjorkman","year":"2000","unstructured":"Bjorkman C, Alenius S, Manuelsson U, Uggla A. Neospora caninum and bovine virus diarrhoea virus infections in Swedish dairy cows in relation to abortion. Vet J. 2000;159:201\u20136.","journal-title":"Vet J."},{"key":"3777_CR62","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.prevetmed.2009.11.012","volume":"94","author":"JA Vanleeuwen","year":"2009","unstructured":"Vanleeuwen JA, Haddad JP, Dohoo IR, Keefe GP, Tiwari A, Tremblay R. Associations between reproductive performance and seropositivity for bovine leukemia virus, bovine viral-diarrhea virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum in Canadian dairy cows. Prev Vet Med. 2009;94:54\u201364.","journal-title":"Prev Vet Med."},{"key":"3777_CR63","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0167-5877(01)00239-2","volume":"52","author":"R Mainar-Jaime","year":"2001","unstructured":"Mainar-Jaime R, Berzal-Herranz B, Arias P, Rojo-V\u00e1zquez F. Epidemiological pattern and risk factors associated with bovine viral-diarrhoea virus (BVDV) infection in a non-vaccinated dairy-cattle population from the Asturias region of Spain. Prev Vet Med. 2001;52:63\u201373.","journal-title":"Prev Vet Med."},{"key":"3777_CR64","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.vetimm.2010.03.006","volume":"136","author":"CP Drew","year":"2010","unstructured":"Drew CP, Heller MC, Mayo C, Watson JL, MacLachlan NJ. Bluetongue virus infection activates bovine monocyte-derived macrophages and pulmonary artery endothelial cells. Vet Immunol Immunopathol. 2010;136:292\u20136.","journal-title":"Vet Immunol Immunopathol."}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-019-3777-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13071-019-3777-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-019-3777-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:23:53Z","timestamp":1604363033000},"score":1,"resource":{"primary":{"URL":"https:\/\/parasitesandvectors.biomedcentral.com\/articles\/10.1186\/s13071-019-3777-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,4]]},"references-count":64,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["3777"],"URL":"https:\/\/doi.org\/10.1186\/s13071-019-3777-0","relation":{},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,4]]},"assertion":[{"value":"5 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures involving animals were approved by PROAE 25\/2016. Spanish (Law 32\/2007, R.D. 53\/2013) and European (Council Directive 2010\/63\/EU) legal requirements and guidelines regarding experimentation and animal welfare were considered to carry out these experiments.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"517"}}