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登革热患者炎症反应的纵向蛋白质组学分析。

Longitudinal proteomic profiling of the inflammatory response in dengue patients.

机构信息

Department of Internal Medicine and the Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia.

出版信息

PLoS Negl Trop Dis. 2023 Jan 3;17(1):e0011041. doi: 10.1371/journal.pntd.0011041. eCollection 2023 Jan.

Abstract

BACKGROUND

The immunopathogenesis of dengue virus (DENV) infection remains incompletely understood. To increase our understanding of inflammatory response in non-severe dengue, we assessed longitudinal changes in the inflammatory proteome in patients with an acute DENV infection.

METHODS

Using a multiplex proximity extension assay (PEA), we measured relative levels of 368 inflammatory markers in plasma samples from hospitalized patients with non-severe DENV infection in the acute (n = 43) and convalescence (n = 35) phase of the infection and samples of healthy controls (n = 10).

RESULTS

We identified 203 upregulated and 39 downregulated proteins in acute versus convalescent plasma samples. The upregulated proteins had a strong representation of interferon (IFN) and IFN-inducible effector proteins, cytokines (e.g. IL-10, IL-33) and cytokine receptors, chemokines, pro-apoptotic proteins (e.g. granzymes) and endothelial markers. A number of differentially expressed proteins (DEPs) have not been reported in previous studies. Functional network analysis highlighted a central role for IFNγ, IL-10, IL-33 and chemokines. We identified different novel associations between inflammatory proteins and circulating concentrations of the endothelial glycocalyx disruption surrogate marker syndecan-1. Conclusion: This unbiased proteome analysis provides a comprehensive insight in the inflammatory response in DENV infection and its association with glycocalyx disruption.

摘要

背景

登革热病毒(DENV)感染的免疫发病机制仍不完全清楚。为了更深入地了解非重症登革热的炎症反应,我们评估了急性 DENV 感染患者中炎症蛋白组的纵向变化。

方法

使用多重邻近延伸分析(PEA),我们测量了住院的非重症 DENV 感染患者急性期(n=43)和恢复期(n=35)及健康对照者(n=10)血浆样本中 368 种炎症标志物的相对水平。

结果

我们在急性期与恢复期血浆样本中鉴定出 203 种上调和 39 种下调蛋白。上调蛋白强烈代表干扰素(IFN)和 IFN 诱导的效应蛋白、细胞因子(如 IL-10、IL-33)和细胞因子受体、趋化因子、促凋亡蛋白(如颗粒酶)和内皮标记物。一些差异表达蛋白(DEPs)在以前的研究中没有报道过。功能网络分析强调了 IFNγ、IL-10、IL-33 和趋化因子的核心作用。我们鉴定了炎症蛋白与内皮糖萼破坏替代标志物 syndecan-1 的循环浓度之间的不同新关联。

结论

这项无偏倚的蛋白质组分析提供了对 DENV 感染中炎症反应及其与糖萼破坏关联的全面了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4375/9838874/42a4b597101b/pntd.0011041.g001.jpg

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