Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination

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 targ...

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Bibliographic Details
Published in:Scientific reports 2017-03, Vol.7 (1), p.43776-43776, Article 43776
Main Authors: Lüdtke, Anja, Ruibal, Paula, Wozniak, David M, Pallasch, Elisa, Wurr, Stephanie, Bockholt, Sabrina, Gómez-Medina, Sergio, Qiu, Xiangguo, Kobinger, Gary P, Rodríguez, Estefanía, Günther, Stephan, Krasemann, Susanne, Idoyaga, Juliana, Oestereich, Lisa, Muñoz-Fontela, César
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - immunology
Antigens, CD - metabolism
CD11b Antigen - immunology
CD11b Antigen - metabolism
Cross-Priming - immunology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - virology
Ebola virus
Ebolavirus - immunology
Ebolavirus - physiology
Epidemics
Hemorrhagic Fever, Ebola - immunology
Hemorrhagic Fever, Ebola - virology
Host-Pathogen Interactions - immunology
Immunology
Infections
Integrin alpha Chains - immunology
Integrin alpha Chains - metabolism
Kinetics
Lymph nodes
Lymphocytes T
Lymphoid Tissue - immunology
Lymphoid Tissue - metabolism
Lymphoid Tissue - virology
Mice, Inbred C57BL
Mice, Knockout
Rodents
T-Lymphocytes - immunology
Viremia - immunology
Viremia - virology
Virus Replication - immunology
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Summary: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 DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep43776