{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:08:57Z","timestamp":1790795337238,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b<jats:sup>+<\/jats:sup> DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103<jats:sup>+<\/jats:sup> DC subset. Furthermore, depletion of CD8 and CD4 T cells resulted in loss of early control of virus replication, viremia and fatal Ebola virus disease (EVD). Thus, our findings point out at T cell function as a key determinant of EVD progress and outcome.<\/jats:p>","DOI":"10.1038\/srep43776","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T12:50:55Z","timestamp":1488545455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination"],"prefix":"10.1038","volume":"7","author":[{"given":"Anja","family":"L\u00fcdtke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Ruibal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Wozniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Pallasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Wurr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Bockholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"G\u00f3mez-Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangguo","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P.","family":"Kobinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Krasemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Idoyaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Oestereich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Mu\u00f1oz-Fontela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"BFsrep43776_CR1","first-page":"e00137","volume":"6","author":"MT Osterholm","year":"2015","unstructured":"Osterholm, M. T. et al. Transmission of Ebola viruses: what we know and what we do not know. MBio 6, e00137 (2015).","journal-title":"MBio"},{"key":"BFsrep43776_CR2","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0140-6736(10)60667-8","volume":"377","author":"H Feldmann","year":"2011","unstructured":"Feldmann, H. & Geisbert, T. W. Ebola haemorrhagic fever. The Lancet 377, 849\u201362 (2011).","journal-title":"The Lancet"},{"key":"BFsrep43776_CR3","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1016\/S0002-9440(10)63591-2","volume":"163","author":"TW Geisbert","year":"2003","unstructured":"Geisbert, T. W. et al. Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am. J. Pathol. 163, 2347\u20132370 (2003).","journal-title":"Am. J. Pathol."},{"key":"BFsrep43776_CR4","doi-asserted-by":"publisher","first-page":"S199","DOI":"10.1086\/514293","volume":"179","author":"EI Ryabchikova","year":"1999","unstructured":"Ryabchikova, E. I., Kolesnikova, L. V. & Luchko, S. V. An analysis of features of pathogenesis in two animal models of Ebola virus infection. J. Infect. Dis. 179 Suppl 1, S199\u2013202 (1999).","journal-title":"J. Infect. Dis."},{"key":"BFsrep43776_CR5","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.4049\/jimmunol.170.6.2797","volume":"170","author":"S Mahanty","year":"2003","unstructured":"Mahanty, S. et al. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J. Immunol. 170, 2797\u20132801 (2003).","journal-title":"J. Immunol."},{"key":"BFsrep43776_CR6","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1086\/379199","volume":"188","author":"CM Bosio","year":"2003","unstructured":"Bosio, C. M. et al. Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation. J. Infect. Dis. 188, 1630\u20131638 (2003).","journal-title":"J. Infect. Dis."},{"key":"BFsrep43776_CR7","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.3390\/v3081501","volume":"3","author":"J Olejnik","year":"2011","unstructured":"Olejnik, J., Ryabchikova, E., Corley, R. B. & M\u00fchlberger, E. Intracellular events and cell fate in filovirus infection. Viruses 3, 1501\u20131531 (2011).","journal-title":"Viruses"},{"key":"BFsrep43776_CR8","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.antiviral.2012.01.011","volume":"93","author":"O Martinez","year":"2012","unstructured":"Martinez, O., Leung, L. W. & Basler, C. F. The role of antigen-presenting cells in filoviral hemorrhagic fever: gaps in current knowledge. Antiviral Res 93, 416\u2013428 (2012).","journal-title":"Antiviral Res"},{"key":"BFsrep43776_CR9","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.3390\/v4091477","volume":"4","author":"SB Bradfute","year":"2012","unstructured":"Bradfute, S. B., Warfield, K. L. & Bray, M. Mouse models for filovirus infections. Viruses 4, 1477\u20131508 (2012).","journal-title":"Viruses"},{"key":"BFsrep43776_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-0-12-417028-5.00001-6","volume":"120","author":"M Haniffa","year":"2013","unstructured":"Haniffa, M., Collin, M. & Ginhoux, F. Ontogeny and functional specialization of dendritic cells in human and mouse. Adv. Immunol. 120, 1\u201349 (2013).","journal-title":"Adv. Immunol."},{"key":"BFsrep43776_CR11","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/icb.2008.14","volume":"86","author":"B Leon","year":"2008","unstructured":"Leon, B. & Ardavin, C. Monocyte-derived dendritic cells in innate and adaptive immunity. Immunol. Cell Biol. 86, 320\u2013324 (2008).","journal-title":"Immunol. Cell Biol."},{"key":"BFsrep43776_CR12","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1099\/0022-1317-82-6-1365","volume":"82","author":"M Bray","year":"2001","unstructured":"Bray, M. The role of the Type I interferon response in the resistance of mice to filovirus infection. J. Gen. Virol. 82, 1365\u20131373 (2001).","journal-title":"J. Gen. Virol."},{"key":"BFsrep43776_CR13","doi-asserted-by":"publisher","first-page":"e1005656","DOI":"10.1371\/journal.ppat.1005656","volume":"12","author":"L Oestereich","year":"2016","unstructured":"Oestereich, L. et al. Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever. PLoS Pathog 12, e1005656 (2016).","journal-title":"PLoS Pathog"},{"key":"BFsrep43776_CR14","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.clim.2011.08.008","volume":"141","author":"X Qiu","year":"2011","unstructured":"Qiu, X. et al. Characterization of Zaire ebolavirus glycoprotein-specific monoclonal antibodies. Clin. Immunol. 141, 218\u2013227 (2011).","journal-title":"Clin. Immunol."},{"key":"BFsrep43776_CR15","doi-asserted-by":"publisher","first-page":"7732","DOI":"10.4049\/jimmunol.0902707","volume":"183","author":"KJ Farrand","year":"2009","unstructured":"Farrand, K. J. et al. Langerin+ CD8alpha+ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens. J. Immunol. 183, 7732\u20137742 (2009).","journal-title":"J. Immunol."},{"key":"BFsrep43776_CR16","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.cell.2010.09.039","volume":"143","author":"C Cheong","year":"2010","unstructured":"Cheong, C. et al. Microbial Stimulation Fully Differentiates Monocytes to DC-SIGN\/CD209(+) Dendritic Cells for Immune T Cell Areas. Cell 143, 416\u2013429 (2010).","journal-title":"Cell"},{"key":"BFsrep43776_CR17","doi-asserted-by":"publisher","first-page":"6841","DOI":"10.1128\/JVI.76.13.6841-6844.2002","volume":"76","author":"CP Alvarez","year":"2002","unstructured":"Alvarez, C. P. et al. C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J. Virol. 76, 6841\u20136844 (2002).","journal-title":"J. Virol."},{"key":"BFsrep43776_CR18","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.immuni.2012.10.016","volume":"38","author":"M Plantinga","year":"2013","unstructured":"Plantinga, M. et al. Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38, 322\u2013335 (2013).","journal-title":"Immunity"},{"key":"BFsrep43776_CR19","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1128\/JVI.02695-12","volume":"87","author":"O Martinez","year":"2013","unstructured":"Martinez, O. et al. Ebola virus exploits a monocyte differentiation program to promote its entry. J. Virol. 87, 3801\u20133814 (2013).","journal-title":"J. Virol."},{"key":"BFsrep43776_CR20","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/ni1309","volume":"7","author":"NV Serbina","year":"2006","unstructured":"Serbina, N. V. & Pamer, E. G. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7, 311\u2013317 (2006).","journal-title":"Nat. Immunol."},{"key":"BFsrep43776_CR21","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.4049\/jimmunol.180.4.2562","volume":"180","author":"KL Lin","year":"2008","unstructured":"Lin, K. L., Suzuki, Y., Nakano, H., Ramsburg, E. & Gunn, M. D. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J. Immunol. 180, 2562\u20132572 (2008).","journal-title":"J. Immunol."},{"key":"BFsrep43776_CR22","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.immuni.2011.09.007","volume":"35","author":"D Hashimoto","year":"2011","unstructured":"Hashimoto, D., Miller, J. & Merad, M. Dendritic cell and macrophage heterogeneity in vivo . Immunity 35, 323\u2013335 (2011).","journal-title":"Immunity"},{"key":"BFsrep43776_CR23","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/j.immuni.2015.05.018","volume":"42","author":"J Helft","year":"2015","unstructured":"Helft, J. et al. GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells. Immunity 42, 1197\u20131211 (2015).","journal-title":"Immunity"},{"key":"BFsrep43776_CR24","doi-asserted-by":"publisher","first-page":"7235","DOI":"10.1128\/JVI.00543-06","volume":"80","author":"M Mohamadzadeh","year":"2006","unstructured":"Mohamadzadeh, M. et al. Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses. J. Virol. 80, 7235\u20137244 (2006).","journal-title":"J. Virol."},{"key":"BFsrep43776_CR25","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/nature20567","volume":"540","author":"CM Ribeiro","year":"2016","unstructured":"Ribeiro, C. M. et al. Receptor usage dictates HIV restriction by human TRIM5\u03b1 in dendritic cell subsets. Nature. 540, 448\u2013452 (2016).","journal-title":"Nature."},{"key":"BFsrep43776_CR26","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/nri2455","volume":"8","author":"M Merad","year":"2008","unstructured":"Merad, M., Ginhoux, F. & Collin, M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8, 935\u2013947 (2008).","journal-title":"Nat. Rev. Immunol."},{"key":"BFsrep43776_CR27","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.immuni.2012.04.012","volume":"37","author":"M Haniffa","year":"2012","unstructured":"Haniffa, M. et al. Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cell. Immunity 37, 60\u201373 (2012).","journal-title":"Immunity"},{"key":"BFsrep43776_CR28","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.1172\/JCI60659","volume":"122","author":"J Helft","year":"2012","unstructured":"Helft, J. et al. Cross-presenting CD103+ dendritic cells are protected from influenza virus infection. J. Clin. Invest. 122, 4037\u20134047 (2012).","journal-title":"J. Clin. Invest."},{"key":"BFsrep43776_CR29","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1089\/jir.2009.0076","volume":"29","author":"CF Basler","year":"2009","unstructured":"Basler, C. F. & Amarasinghe, G. K. Evasion of interferon responses by Ebola and Marburg viruses. J. Interferon Cytokine Res. 29, 511\u2013520 (2009).","journal-title":"J. Interferon Cytokine Res."},{"key":"BFsrep43776_CR30","doi-asserted-by":"publisher","first-page":"7945","DOI":"10.1128\/JVI.77.14.7945-7956.2003","volume":"77","author":"CF Basler","year":"2003","unstructured":"Basler, C. F. et al. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. journal of Virology 77, 7945\u20137956 (2003).","journal-title":"journal of Virology"},{"key":"BFsrep43776_CR31","doi-asserted-by":"publisher","first-page":"7567","DOI":"10.1128\/JVI.00924-15","volume":"89","author":"PA Ilinykh","year":"2015","unstructured":"Ilinykh, P. A. et al. Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene Expression in Human Dendritic Cells. J. Virol. 89, 7567\u20137583 (2015).","journal-title":"J. Virol."},{"key":"BFsrep43776_CR32","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nature17949","volume":"533","author":"P Ruibal","year":"2016","unstructured":"Ruibal, P. et al. Unique human immune signature of Ebola virus disease in Guinea. Nature 533, 100\u2013104 (2016).","journal-title":"Nature"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep43776","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep43776.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep43776.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T19:09:00Z","timestamp":1671822540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep43776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,3]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,20]]}},"alternative-id":["BFsrep43776"],"URL":"https:\/\/doi.org\/10.1038\/srep43776","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,3]]},"assertion":[{"value":"17 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43776"}}