tetano
Editor, Senior Moderator
Front Immunol. 2019 Dec 6;10:2867. doi: 10.3389/fimmu.2019.02867. eCollection 2019. [h=1]CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections.[/h]
Sung PS[SUP]1[/SUP], Hsieh SL[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h] 1 Genomics Research Center, Academia Sinica, Taipei, Taiwan. 2 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 3 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. 4 Institute for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
[h=3]Abstract[/h] The protective roles of endosomal toll-like receptors (TLRs) and cytosolic nucleic acid sensors are well elucidated, but the pathogenic host factors during viral infections remain unclear. Spleen tyrosine kinase (Syk)-coupled C-type lectins (CLECs) CLEC2 and CLEC5A are highly expressed on platelets and myeloid cells, respectively. CLEC2 has been shown to recognize snake venom aggretin and the endogenous ligand podoplanin and acts as a critical regulator in the development and immunothrombosis. Although CLEC2 has been reported to interact with type I immunodeficiency virus (HIV-1), its role in viral infections is still unclear. CLEC5A binds to fucose and mannose moieties of dengue virus membrane glycans, as well as to N-acetylglucosamine (GlcNAc)/N-acetylmuramic acid (MurNAc) disaccharides that form the backbone of L. monocytogenes peptidoglycans. Recently, we demonstrated that both CLEC2 and CLEC5A are critical in microbe-induced "neutrophil extracellular trap" (NET) formation and proinflammatory cytokine production. Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). These findings not only illustrate the immunomodulatory effects of EVs during platelet-leukocyte interactions, but also demonstrate the critical roles of CLEC2 and CLEC5A in acute viral infections.
Copyright ? 2019 Sung and Hsieh.
[h=4]KEYWORDS:[/h] CLEC2; CLEC5A; Syk; TLR; exosome; extracellular vesicle; microvesicle
PMID: 31867016 PMCID: PMC6909378 DOI: 10.3389/fimmu.2019.02867
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Sung PS[SUP]1[/SUP], Hsieh SL[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h] 1 Genomics Research Center, Academia Sinica, Taipei, Taiwan. 2 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 3 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. 4 Institute for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
[h=3]Abstract[/h] The protective roles of endosomal toll-like receptors (TLRs) and cytosolic nucleic acid sensors are well elucidated, but the pathogenic host factors during viral infections remain unclear. Spleen tyrosine kinase (Syk)-coupled C-type lectins (CLECs) CLEC2 and CLEC5A are highly expressed on platelets and myeloid cells, respectively. CLEC2 has been shown to recognize snake venom aggretin and the endogenous ligand podoplanin and acts as a critical regulator in the development and immunothrombosis. Although CLEC2 has been reported to interact with type I immunodeficiency virus (HIV-1), its role in viral infections is still unclear. CLEC5A binds to fucose and mannose moieties of dengue virus membrane glycans, as well as to N-acetylglucosamine (GlcNAc)/N-acetylmuramic acid (MurNAc) disaccharides that form the backbone of L. monocytogenes peptidoglycans. Recently, we demonstrated that both CLEC2 and CLEC5A are critical in microbe-induced "neutrophil extracellular trap" (NET) formation and proinflammatory cytokine production. Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). These findings not only illustrate the immunomodulatory effects of EVs during platelet-leukocyte interactions, but also demonstrate the critical roles of CLEC2 and CLEC5A in acute viral infections.
Copyright ? 2019 Sung and Hsieh.
[h=4]KEYWORDS:[/h] CLEC2; CLEC5A; Syk; TLR; exosome; extracellular vesicle; microvesicle
PMID: 31867016 PMCID: PMC6909378 DOI: 10.3389/fimmu.2019.02867
Free full text