Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/85405
Title: Dengue virus-infected dendritic cells, but not monocytes, activate natural killer cells through a contact-dependent mechanism involving adhesion molecules
Authors: Costa, Vivian Vasconcelos
Ye, Weijian
Chen, Qingfeng
Teixeira, Mauro Martins
Preiser, Peter
Ooi, Eng Eong
Chen, Jianzhu
Keywords: Dengue Virus
Adhesion Molecule
Science::Biological sciences
Issue Date: 2017
Source: Costa, 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.00741-17
Series/Report no.: mBio
Abstract: Natural 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.
URI: https://hdl.handle.net/10356/85405
http://hdl.handle.net/10220/50195
DOI: 10.1128/mBio.00741-17
Rights: © 2017 Costa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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