美国斯坦福大学医学院Shirit Einav等研究人员合作通过系统免疫学方法确定严重登革热进展的全局和细胞类型特异性免疫特征。相关论文于2023年10月23日在线发表在《自然—免疫学》杂志上。

为了确定儿童血液中登革病毒（DENV）的靶细胞和严重登革热（SD）进展的免疫学特征，研究人员整合了两种捕获细胞和病毒元件的单细胞方法：包含病毒的单细胞RNA测序（viscRNA-Seq 2）和带有分泌组分析和功能测试的靶向蛋白质组学。除了髓系细胞外，在自然感染中，B细胞也蕴藏着能感染许可细胞的复制DENV。细胞类型丰度、基因和蛋白质表达与分泌以及细胞间通讯的改变表明，SD进展者的免疫细胞迁移和炎症反应加剧。

同时，SD进展者的抗原递呈细胞显示出完整的摄取，但干扰素反应和抗原处理及递呈特征受损，这些特征部分受DENV调节。SD进展者的特征还包括效应反应的激活、调节和耗竭增加，以及HLA-DR表达的适应性类NK细胞的扩增。这些发现揭示了人体血液中的DENV靶细胞，并提供了对抗体介导的增强之外的SD发病机制见解。

据了解，SD是发病和死亡的主要原因。

附：英文原文

Title: Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach

Author: Ghita, Luca, Yao, Zhiyuan, Xie, Yike, Duran, Veronica, Cagirici, Halise Busra, Samir, Jerome, Osman, Ilham, Rebelln-Snchez, David Esteban, Agudelo-Rojas, Olga Lucia, Sanz, Ana Maria, Sahoo, Malaya Kumar, Robinson, Makeda L., Gelvez-Ramirez, Rosa Margarita, Bueno, Nathalia, Luciani, Fabio, Pinsky, Benjamin A., Montoya, Jose G., Estupian-Cardenas, Maria Isabel, Villar-Centeno, Luis Angel, Rojas-Garrido, Elsa Marina, Rosso, Fernando, Quake, Stephen R., Zanini, Fabio, Einav, Shirit

Issue&Volume: 2023-10-23

Abstract: Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children’s blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell–cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

DOI: 10.1038/s41590-023-01654-3

Source: https://www.nature.com/articles/s41590-023-01654-3