Journal article
Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 2.3MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41467-017-02083-1
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 8
- Issue:
- 1
- Pages:
- 1985
- Publication date:
- 2017-12-07
- Acceptance date:
- 2017-11-06
- DOI:
- EISSN:
-
2041-1723
- ISSN:
-
2041-1723
- Pmid:
-
29215015
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:911181
- UUID:
-
uuid:7d8b17a9-0640-4db8-a9e5-c24d7ffe641d
- Local pid:
-
pubs:911181
- Source identifiers:
-
911181
- Deposit date:
-
2018-08-30
- ARK identifier:
Terms of use
- Copyright holder:
- Sampaio et al
- Copyright date:
- 2017
- Notes:
- © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record