Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Front Immunol. 2022 Sep 15;13:958820. doi: 10.3389/fimmu.2022.958820. eCollection 2022.
Chikungunya fever is a viral disease transmitted by mosquitoes of the genus Aedes. The infection is usually symptomatic and most common symptoms are fever accompanied by joint pain and swelling. In most cases symptoms subside within a week. However, severe prolonged and disabling joint pain, that may persist for several months, even years, are reported. Although the pathogenesis of Chikungunya infection is not fully understood, the evolution to severe disease seems to be associated with the activation of immune mechanisms and the action of inflammatory mediators. Platelets are recognized as inflammatory cells with fundamental activities in the immune response, maintenance of vascular stability and pathogenicity of several inflammatory and infectious diseases. Although the involvement of platelets in the pathogenesis of viral diseases has gained attention in recent years, their activation in Chikungunya has not been explored. The aim of this study was to analyze platelet activation and the possible role of platelets in the amplification of the inflammatory response during Chikungunya infection. We prospectively included 132 patients attended at the Quinta D'Or hospital and 25 healthy volunteers during the 2016 epidemic in Rio de Janeiro, Brazil. We observed increased expression of CD62P on the surface of platelets, as well as increased plasma levels of CD62P and platelet-derived inflammatory mediators indicating that the Chikungunya infection leads to platelet activation. In addition, platelets from chikungunya patients exhibit increased expression of NLRP3, caspase 4, and cleaved IL-1β, suggestive of platelet-inflammasome engagement during chikungunya infection. experiments confirmed that the Chikungunya virus directly activates platelets. Moreover, we observed that platelet activation and soluble p-selectin at the onset of symptoms were associated with development of chronic forms of the disease. Collectively, our data suggest platelet involvement in the immune processes and inflammatory amplification triggered by the infection.
基孔肯雅热是一种由伊蚊属蚊子传播的病毒性疾病。感染通常有症状，最常见的症状是发热伴关节疼痛和肿胀。大多数情况下，症状会在一周内消退。然而，据报道，严重的、长期的和致残性的关节疼痛可能会持续数月甚至数年。虽然基孔肯雅热感染的发病机制尚未完全阐明，但向严重疾病的演变似乎与免疫机制的激活和炎症介质的作用有关。血小板被认为是具有免疫反应、血管稳定性维持和几种炎症和感染性疾病发病机制的基本作用的炎症细胞。尽管近年来血小板在病毒病发病机制中的作用受到关注，但它们在基孔肯雅热中的激活尚未得到探索。本研究旨在分析血小板激活以及血小板在基孔肯雅热感染期间放大炎症反应中的可能作用。我们前瞻性地纳入了 2016 年巴西里约热内卢基孔肯雅热流行期间在 Quinta D'Or 医院就诊的 132 名患者和 25 名健康志愿者。我们观察到血小板表面 CD62P 的表达增加，以及血浆 CD62P 和血小板衍生炎症介质水平升高，表明基孔肯雅热感染导致血小板激活。此外，来自基孔肯雅热患者的血小板表现出 NLRP3、 caspase 4 和切割的 IL-1β 的表达增加，提示在基孔肯雅热感染期间血小板-炎症小体的参与。 实验证实，基孔肯雅病毒可直接激活血小板。此外，我们观察到症状发作时血小板激活和可溶性 p-选择素与慢性疾病的发生有关。总的来说，我们的数据表明血小板参与了感染引发的免疫过程和炎症放大。
