Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1007298
Title: Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway
Authors: Ye W.
Chew M.
Hou J.
Lai F. 
Leopold S.J.
Loo H.L.
Ghose A.
Dutta A.K.
Chen Q. 
Ooi E.E. 
White N.J.
Dondorp A.M.
Preiser P.
Chen J. 
Keywords: bilirubin
CD69 antigen
creatinine
gamma interferon
granulysin
interferon induced helicase C domain containing protein 1
interleukin 2 receptor alpha
lectin receptor
lysosome associated membrane protein 1
natural killer cell receptor NKG2A
natural killer cell receptor NKG2D
IFIH1 protein, human
interferon induced helicase C domain containing protein 1
adult
Article
cell heterogeneity
confocal microscopy
controlled study
cytotoxicity
discriminant analysis
erythrocyte
female
flow cytometry
gel electrophoresis
gene expression
hematocrit
human
human cell
hypoglycemia
immune response
immunoassay
malaria
male
membrane microparticle
microarray analysis
natural killer T cell
parasitemia
peripheral blood mononuclear cell
Plasmodium falciparum
protein expression
respiratory failure
reverse transcription
RNA isolation
signal transduction
systolic blood pressure
Western blotting
antagonists and inhibitors
cell culture
CRISPR Cas system
cytoplasm
erythrocyte
genetics
immunology
isolation and purification
lymphocyte activation
malaria falciparum
membrane microparticle
metabolism
natural killer cell
parasitology
Cell-Derived Microparticles
Cells, Cultured
CRISPR-Cas Systems
Cytoplasm
Erythrocytes
Humans
Interferon-Induced Helicase, IFIH1
Killer Cells, Natural
Lymphocyte Activation
Malaria, Falciparum
Plasmodium falciparum
Issue Date: 2018
Citation: Ye W., Chew M., Hou J., Lai F., Leopold S.J., Loo H.L., Ghose A., Dutta A.K., Chen Q., Ooi E.E., White N.J., Dondorp A.M., Preiser P., Chen J. (2018). Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway. PLoS Pathogens 14 (10) : e1007298. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1007298
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-? secretion, lysis of iRBCs. Similarly, inhibition of TBK1/IKK�, 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. ? 2018 Ye et al. http://creativecommons.org/licenses/by/4.0/.
Source Title: PLoS Pathogens
URI: https://scholarbank.nus.edu.sg/handle/10635/161879
ISSN: 15537366
DOI: 10.1371/journal.ppat.1007298
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