Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors
Sisquella, Xavier, Ofir-Birin, Yifat, Pimentel, Matthew A., Cheng, Lesley, Abou Karam, Paula, Sampaio, Natalia G., Penington, Jocelyn Sistema, Connolly, Dympna, Giladi, Tal, Scicluna, Benjamin J., Sharples, Robyn A., Waltmann, Andreea, Avni, Dror, Schwartz, Eli, Schofield, Louis, Porat, Ziv, Hansen, Diana S., Papenfuss, Anthony T., Eriksson, Emily M., Gerlic, Motti, Hill, Andrew, Bowie, Andrew G., and Regev-Rudzki, Neta (2017) Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors. Nature Communications, 8. 1985.
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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.
| Item ID: | 51888 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 2041-1723 |
| Additional Information: | Open Access. 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/. |
| Funders: | Israel Science Foundation (ISF), National Institutes of Health (NIH), Science Foundation, Israel (SFI) |
| Projects and Grants: | ISF grant #1416/15, NIH AI093752, SFI 11/PI/056 |
| Date Deposited: | 27 Dec 2017 07:39 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 50% |
| SEO Codes: | 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50% |
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