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dc.contributor.authorYe, Weijianen
dc.contributor.authorChew, Marvinen
dc.contributor.authorHou, Jueen
dc.contributor.authorLai, Fritzen
dc.contributor.authorLeopold, Stije J.en
dc.contributor.authorLoo, Hooi Linnen
dc.contributor.authorGhose, Aniruddhaen
dc.contributor.authorDutta, Ashok K.en
dc.contributor.authorChen, Qingfengen
dc.contributor.authorOoi, Eng Eongen
dc.contributor.authorWhite, Nicholas J.en
dc.contributor.authorDondorp, Arjen M.en
dc.contributor.authorPreiser, Peteren
dc.contributor.authorChen, Jianzhuen
dc.contributor.editorGoodier, Martinen
dc.identifier.citationYe, 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.1007298en
dc.description.abstractNatural 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.en
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en
dc.format.extent21 p.en
dc.relation.ispartofseriesPLOS Pathogensen
dc.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.en
dc.subjectNK Cellsen
dc.subjectDRNTU::Science::Biological sciencesen
dc.titleMicrovesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathwayen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.contributor.researchSingapore-MIT Alliance Programmeen
dc.description.versionPublished versionen
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