Disease Biology Laboratory, Regional Center for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.
School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, India.
Front Cell Infect Microbiol. 2020 Sep 30;10:561366. doi: 10.3389/fcimb.2020.561366. eCollection 2020.
Platelets are anucleated blood cells derived from bone marrow megakaryocytes and play a crucial role in hemostasis and thrombosis. Platelets contain specialized storage organelles, called alpha-granules, contents of which are rich in cytokines such as C-X-C Motif Chemokine Ligand (CXCL) 1/4/7, (C-C motif) ligand (CCL) 5/3, CXCL8 (also called as interleukin 8, IL-8), and transforming growth factor β (TGF-β). Activation of platelets lead to degranulation and release of contents into the plasma. Platelet activation is a common event in many viral infections including human immunodeficiency virus (HIV), H1N1 influenza, Hepatitis C virus (HCV), Ebola virus (EBV), and Dengue virus (DENV). The cytokines CXCL8, CCL5 (also known as Regulated on Activation, Normal T Expressed and Secreted, RANTES), tumor necrosis factor α (TNF-α), CXCL1/5 and CCL3 released, promote development of a pro-inflammatory state along with the recruitment of other immune cells to the site of infection. Platelets also interact with Monocytes and Neutrophils and facilitate their activation to release different cytokines which further enhances inflammation. Upon activation, platelets also secrete factors such as CXCL4 (also known as platelet factor, PF4), CCL5 and fibrinopeptides which are critical regulators of replication and propagation of several viruses in the host. Studies suggest that CXCL4 can both inhibit as well as enhance HIV1 infection. Data from our lab show that CXCL4 inhibits interferon (IFN) pathway and promotes DENV replication in monocytes and in patients significantly. Inhibition of CXCL4 mediated signaling results in increased IFN production and suppressed DENV and JEV replication in monocytes. In this review, we discuss the role of platelets in viral disease progression with a focus on dengue infection.
血小板是骨髓巨核细胞衍生而来的无核血细胞，在止血和血栓形成中发挥着关键作用。血小板含有专门的储存细胞器，称为α-颗粒，其内容物富含细胞因子，如 C-X-C 基序趋化因子配体（CXCL）1/4/7、（C-C 基序）配体（CCL）5/3、CXCL8（也称为白细胞介素 8，IL-8）和转化生长因子-β（TGF-β）。血小板的激活导致脱颗粒并将内容物释放到血浆中。血小板的激活是许多病毒感染（包括人类免疫缺陷病毒（HIV）、H1N1 流感、丙型肝炎病毒（HCV）、埃博拉病毒（EBV）和登革热病毒（DENV））中的常见事件。释放的细胞因子 CXCL8、CCL5（也称为激活、正常 T 表达和分泌，RANTES）、肿瘤坏死因子-α（TNF-α）、CXCL1/5 和 CCL3，促进了促炎状态的发展，并招募其他免疫细胞到感染部位。血小板还与单核细胞和中性粒细胞相互作用，并促进它们的激活以释放进一步增强炎症的不同细胞因子。血小板激活后还会分泌 CXCL4（也称为血小板因子，PF4）、CCL5 和纤维蛋白肽等因子，这些因子是宿主中几种病毒复制和传播的关键调节剂。研究表明，CXCL4 既能抑制又能增强 HIV1 感染。我们实验室的数据表明，CXCL4 抑制干扰素（IFN）途径并促进单核细胞中 DENV 的复制，并且在患者中也显著促进 DENV 的复制。CXCL4 介导的信号转导的抑制导致 IFN 产生增加，并抑制单核细胞中 DENV 和 JEV 的复制。在这篇综述中，我们讨论了血小板在病毒疾病进展中的作用，重点讨论了登革热感染。
