Department of Medicine, Division of Cardiovascular Medicine, 368 Plantation Street, Worcester, MA, 01605, USA.
Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Polo Unico Sant'Andrea delle Fratte, Perugia, 06132, Italy.
Nat Commun. 2019 Apr 16;10(1):1780. doi: 10.1038/s41467-019-09607-x.
Influenza infection increases the incidence of myocardial infarction but the reason is unknown. Platelets mediate vascular occlusion through thrombotic functions but are also recognized to have immunomodulatory activity. To determine if platelet processes are activated during influenza infection, we collected blood from 18 patients with acute influenza infection. Microscopy reveals activated platelets, many containing viral particles and extracellular-DNA associated with platelets. To understand the mechanism, we isolate human platelets and treat them with influenza A virus. Viral-engulfment leads to C3 release from platelets as a function of TLR7 and C3 leads to neutrophil-DNA release and aggregation. TLR7 specificity is confirmed in murine models lacking the receptor, and platelet depletion models support platelet-mediated C3 and neutrophil-DNA release post-influenza infection. These findings demonstrate that the initial intrinsic defense against influenza is mediated by platelet-neutrophil cross-communication that tightly regulates host immune and complement responses but can also lead to thrombotic vascular occlusion.
流感感染会增加心肌梗死的发病率，但原因尚不清楚。血小板通过血栓形成功能介导血管闭塞，但也被认为具有免疫调节活性。为了确定血小板过程是否在流感感染期间被激活，我们从 18 名急性流感感染患者中采集血液。显微镜显示活化的血小板，其中许多血小板含有病毒颗粒和与血小板相关的细胞外 DNA。为了了解其机制，我们分离了人类血小板并用流感 A 病毒进行处理。病毒吞噬作用导致血小板释放 C3，这是 TLR7 的功能，而 C3 导致中性粒细胞 DNA 释放和聚集。在缺乏受体的小鼠模型中证实了 TLR7 的特异性，并且血小板耗竭模型支持流感感染后血小板介导的 C3 和中性粒细胞 DNA 释放。这些发现表明，针对流感的初始固有防御是由血小板-中性粒细胞交叉通讯介导的，这种通讯严格调节宿主免疫和补体反应，但也可能导致血栓性血管闭塞。
