Immune profiling in subclinical secondary dengue-infected cases reveals adaptive immune signatures correlated to protection from severe dengue

IF 18.7 1区医学 Q1 MICROBIOLOGY

Cell host & microbe Pub Date : 2025-06-27 DOI:10.1016/j.chom.2025.06.006

Giorgio Gonnella, Valentina Libri, Emanuele Gioacchino, Sébastien Mella, Sotheary Sann, Sopheak Sorn, Sreymom Ken, Valerie Seffer, Nisa Ya, Leangyi Heng, Chantana Yay, Anavaj Sakuntabhai, Sowath Ly, Philippe Dussart, Veasna Duong, Milena Hasan, Tineke Cantaert

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引用次数: 0

Abstract

Development of strategies to prevent severe dengue has been challenging, partly by our incomplete understanding of a protective immune response after dengue virus (DENV) infection. To define adaptive immune signatures associated with protection from hospitalized dengue, we performed in-depth single-cell immunoprofiling and quantified DENV-specific T cells in subclinical or hospitalized dengue-infected children. Individuals with subclinical infection exhibit clonally expanded CD4+ TEMRA cells, increased frequency of DENV-specific CD4+ T cells, and demonstrate a gene expression signature of increased Treg functionality. Across all T cell subsets, subclinical cases upregulated a type I IFN response gene signature. In contrast, expanding CD8+ EM cells from hospitalized patients express more inhibitory markers and fewer cytotoxic proteins. In addition, hospitalized dengue is characterized by high frequencies and clonally expanded immunoglobulin G (Ig)G1-expressing plasmablasts. These findings identify candidate correlates of protection and support a rationale for T cell-directed interventions for dengue disease.

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亚临床继发性登革热感染病例的免疫分析揭示了与严重登革热保护相关的适应性免疫特征

制定预防重症登革热的战略一直具有挑战性，部分原因是我们对登革热病毒（DENV）感染后的保护性免疫反应了解不完全。为了确定与住院登革热保护相关的适应性免疫特征，我们在亚临床或住院登革热感染儿童中进行了深入的单细胞免疫分析和定量denv特异性T细胞。亚临床感染个体表现出CD4+ TEMRA细胞的克隆扩增，denv特异性CD4+ T细胞的频率增加，并表现出Treg功能增加的基因表达特征。在所有T细胞亚群中，亚临床病例上调I型IFN反应基因特征。相比之下，来自住院患者的扩增CD8+ EM细胞表达更多的抑制标记物和更少的细胞毒性蛋白。此外，住院登革热的特点是高频率和克隆扩增的表达免疫球蛋白G (Ig) g1的质母细胞。这些发现确定了保护的候选相关因素，并支持T细胞定向干预登革热疾病的基本原理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell host & microbe 生物-微生物学

CiteScore

45.10

自引率

1.70%

发文量

201

审稿时长

4-8 weeks

期刊介绍： Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.