Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors
Citation:
Sisquella, X. and Ofir-Birin, Y. and Pimentel, M.A. and Cheng, L. and Abou Karam, P. and Sampaio, N.G. and Penington, J.S. and Connolly, D. and Giladi, T. and Scicluna, B.J. and Sharples, R.A. and Waltmann, A. and Avni, D. and Schwartz, E. and Schofield, L. and Porat, Z. and Hansen, D.S. and Papenfuss, A.T. and Eriksson, E.M. and Gerlic, M. and Hill, A.F. and Bowie, A.G. and Regev-Rudzki, N., Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors, Nature Communications, 8, 1, 2017, 1985-Download Item:
Abstract:
STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria parasite
(
Plasmodium falciparum
) or other pathogen DNA. As
P. falciparum
infects red blood cells and
not leukocytes, how parasite DNA reaches such host cytosolic DNA sensors in immune cells
is unclear. Here we show that malaria parasites inside red blood cells can engage host
cytosolic innate immune cell receptors from a distance by secreting extracellular vesicles
(EV) containing parasitic small RNA and genomic DNA. Upon internalization of DNA-
harboring EVs by human monocytes,
P. falciparum
DNA is released within the host cell
cytosol, leading to STING-dependent DNA sensing. STING subsequently activates the kinase
TBK1, which phosphorylates the transcription factor IRF3, causing IRF3 to translocate to the
nucleus and induce STING-dependent gene expression. This DNA-sensing pathway may be
an important decoy mechanism to promote
P. falciparum
virulence and thereby may affect
future strategies to treat malaria.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
11/PI/1056
Author's Homepage:
http://people.tcd.ie/agbowie
Author: BOWIE, ANDREW
Type of material:
Journal ArticleCollections
Series/Report no:
Nature Communications;8;
1;
Availability:
Full text availableKeywords:
MalariaDOI:
http://dx.doi.org/10.1038/s41467-017-02083-1Metadata
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