期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-10360-4
关键词
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资金
- Academia Sinica [106-2101-01-11-01, 107-2101-01-18-03, AS-TP-106-L11, AS-TP-106-L11-1]
- Ministry of Science and Technology [MOST 107-2321-B-001-015, MOST 106-2320-B-001-023-MY3]
- Summit and Thematic Research Projects (Academia Sinica)
- VGH [VTA107-V2-1-2]
- TSGH [VTA107-V2-1-2]
- AS Joint Research Program [VTA107-V2-1-2]
- National Research Program for Genomic Medicine (NRPGM) at the National Science Council of Taiwan
Platelet-leukocyte interactions amplify inflammatory reactions, but the underlying mechanism is still unclear. CLEC5A and CLEC2 are spleen tyrosine kinase (Syk)-coupled C-type lectin receptors, abundantly expressed by leukocytes and platelets, respectively. Whereas CLEC5A is a pattern recognition receptor (PRR) to flaviviruses and bacteria, CLEC2 is the receptor for platelet-activating snake venom aggretin. Here we show that dengue virus (DV) activates platelets via CLEC2 to release extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles (MVs). DV-induced EXOs (DV-EXOs) and MVs (DV-MVs) further activate CLEC5A and TLR2 on neutrophils and macrophages, thereby induce neutrophil extracellular trap (NET) formation and proinflammatory cytokine release. Compared to stat1(-/-) mice, simultaneous blockade of CLEC5A and TLR2 effectively attenuates DV-induced inflammatory response and increases survival rate from 30 to 90%. The identification of critical roles of CLEC2 and CLEC5A/TLR2 in platelet-leukocyte interactions will support the development of novel strategies to treat acute viral infection in the future.
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