Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/106329
Title: Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway
Authors: Ye, Weijian
Chew, Marvin
Hou, Jue
Lai, Fritz
Leopold, Stije J.
Loo, Hooi Linn
Ghose, Aniruddha
Dutta, Ashok K.
Chen, Qingfeng
Ooi, Eng Eong
White, Nicholas J.
Dondorp, Arjen M.
Preiser, Peter
Chen, Jianzhu
Keywords: NK Cells
Malaria
DRNTU::Science::Biological sciences
Issue Date: 2018
Source: Ye, W., Chew, M., Hou, J., Lai, F., Leopold, S. J., Loo, H. L., . . . Chen, J. (2018). Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway. PLOS Pathogens, 14(10), e1007298-. doi:10.1371/journal.ppat.1007298
Series/Report no.: PLOS Pathogens
Abstract: Natural killer (NK) cells provide the first line of defense against malaria parasite infection. However, the molecular mechanisms through which NK cells are activated by parasites are largely unknown, so is the molecular basis underlying the variation in NK cell responses to malaria infection in the human population. Here, we compared transcriptional profiles of responding and non-responding NK cells following exposure to Plasmodium-infected red blood cells (iRBCs) and identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be differentially expressed. Knockout of MDA5 in responding human NK cells by CRISPR/cas9 abolished NK cell activation, IFN-γ secretion, lysis of iRBCs. Similarly, inhibition of TBK1/IKKε, an effector molecule downstream of MDA5, also inhibited activation of responding NK cells. Conversely, activation of MDA5 by liposome-packaged poly I:C restored non-responding NK cells to lyse iRBCs. We further show that microvesicles containing large parasite RNAs from iRBCs activated NK cells by fusing with NK cells. These findings suggest that NK cells are activated through the MDA5 pathway by parasite RNAs that are delivered to the cytoplasm of NK cells by microvesicles from iRBCs. The difference in MDA5 expression between responding and non-responding NK cells following exposure to iRBCs likely contributes to the variation in NK cell responses to malaria infection in the human population.
URI: https://hdl.handle.net/10356/106329
http://hdl.handle.net/10220/47420
ISSN: 1553-7366
DOI: 10.1371/journal.ppat.1007298
Rights: © 2018 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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