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dc.contributor.authorCosta, Vivian Vasconcelosen
dc.contributor.authorYe, Weijianen
dc.contributor.authorChen, Qingfengen
dc.contributor.authorTeixeira, Mauro Martinsen
dc.contributor.authorPreiser, Peteren
dc.contributor.authorOoi, Eng Eongen
dc.contributor.authorChen, Jianzhuen
dc.contributor.editorPalese, Peteren
dc.identifier.citationCosta, V. V., Ye, W., Chen, Q., Teixeira, M. M., Preiser, P., Ooi, E. E., & Chen, J. (2017). Dengue virus-infected dendritic cells, but not monocytes, activate natural killer cells through a contact-dependent mechanism involving adhesion molecules. mBio, 8(4), e00741-17-. doi:10.1128/mBio.00741-17en
dc.description.abstractNatural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo, identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection.en
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en
dc.format.extent14 p.en
dc.rights© 2017 Costa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en
dc.subjectDengue Virusen
dc.subjectAdhesion Moleculeen
dc.subjectScience::Biological sciencesen
dc.titleDengue virus-infected dendritic cells, but not monocytes, activate natural killer cells through a contact-dependent mechanism involving adhesion moleculesen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.description.versionPublished versionen
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