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基孔肯雅热中的单核细胞动态变化:持续激活与血管凝血途径参与

Monocyte Dynamics in Chikungunya Fever: Sustained Activation and Vascular-Coagulation Pathway Involvement.

作者信息

Dos Santos Caroline Fernandes, Nunes Priscila Conrado Guerra, Fiestas-Solorzano Victor Edgar, Gandini Mariana, Dos Santos Flavia Barreto, Pinheiro Roberta Olmo, de Souza Luís Jose, Damasco Paulo Vieira, de Oliveira Pinto Luzia Maria, de Azeredo Elzinandes Leal

机构信息

Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.

Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.

出版信息

Viruses. 2025 Sep 7;17(9):1224. doi: 10.3390/v17091224.

DOI:10.3390/v17091224
PMID:41012652
Abstract

Chikungunya fever (CF), caused by the Chikungunya virus (CHIKV), is characterized by disabling symptoms such as joint pain that can last for months. Monocytes play a central role in immune modulation and viral replication during infection. This study evaluated the clinical and immunological profiles of patients with laboratory-confirmed CF. Fever and joint pain were the most frequently reported symptoms, whereas edema was more common in women. CHIKV-infect individuals exhibited increased TLR4 expression in non-classical monocytes (CD14+CD16++). Additionally, intermediate (CD14+CD16+) and non-classical (CD14+CD16++) monocytes expressing TLR7 were enriched during the acute phase and in some chronic patients, thereby suggest prolonged TLR7 pathway activation. Levels of soluble CD163 (sCD163)-a marker of monocyte/macrophage activation-were elevated as well, indicating sustained immune activation. Coagulation-related mediators-including Tissue factor (TF) and Tissue factor pathway inhibitor (TFPI)-also increased, despite the rarity of hemorrhagic events or thrombocytopenia. Patients with arthritis demonstrated higher frequencies of TLR7+ intermediate monocytes and elevated Epidermal growth factor (EGF) levels, whereas those with edema exhibit increased Vascular endothelial growth factor (VEGF) levels. Overall, these findings highlighted the differential activation of CD16+ monocytes and suggested that sCD163 is a marker of monocyte/macrophage activation during CHIKV infection.

摘要

基孔肯雅热(CF)由基孔肯雅病毒(CHIKV)引起,其特征为出现诸如关节疼痛等致残症状,且疼痛可持续数月。单核细胞在感染期间的免疫调节和病毒复制中起核心作用。本研究评估了实验室确诊的CF患者的临床和免疫学特征。发热和关节疼痛是最常报告的症状,而水肿在女性中更为常见。感染CHIKV的个体在非经典单核细胞(CD14+CD16++)中表现出TLR4表达增加。此外,表达TLR7的中间型(CD14+CD16+)和非经典型(CD14+CD16++)单核细胞在急性期和一些慢性患者中增多,从而提示TLR7途径的激活持续存在。可溶性CD163(sCD163)——单核细胞/巨噬细胞激活的标志物——水平也升高,表明免疫激活持续存在。尽管出血事件或血小板减少症罕见,但包括组织因子(TF)和组织因子途径抑制剂(TFPI)在内的凝血相关介质也增加。患有关节炎的患者表现出较高频率的TLR7+中间型单核细胞和升高的表皮生长因子(EGF)水平,而患有水肿的患者表现出血管内皮生长因子(VEGF)水平升高。总体而言,这些发现突出了CD16+单核细胞的差异激活,并表明sCD163是CHIKV感染期间单核细胞/巨噬细胞激活的标志物。

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本文引用的文献

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Acute Chikungunya Infection Induces Vascular Dysfunction by Directly Disrupting Redox Signaling in Endothelial Cells.急性基孔肯雅热感染通过直接破坏内皮细胞中的氧化还原信号诱导血管功能障碍。
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Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis.
人源小胶质细胞 C20 中感染基孔肯雅病毒诱导线粒体介导的细胞凋亡。
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Ly6C monocytes in the skin promote systemic alphavirus dissemination.皮肤中的 Ly6C 单核细胞促进全身性甲病毒传播。
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Predictors of chronic joint pain after Chikungunya virus infection in the INOVACHIK prospective cohort study.在INOVACHIK前瞻性队列研究中,基孔肯雅病毒感染后慢性关节疼痛的预测因素。
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Monocyte-endothelial cell interactions in vascular and tissue remodeling.单核细胞-内皮细胞相互作用与血管和组织重构。
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Innate immune response in patients with acute Chikungunya disease.急性基孔肯雅热患者的固有免疫应答。
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TLR4 is one of the receptors for Chikungunya virus envelope protein E2 and regulates virus induced pro-inflammatory responses in host macrophages.Toll 样受体 4 是基孔肯雅病毒包膜蛋白 E2 的受体之一,调节宿主巨噬细胞中病毒诱导的促炎反应。
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