Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics.
Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics.
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DOI：
10.1126/sciadv.ade7702
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发表时间：
2023-03-24
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
每年约有500万登革热病毒感染患者进展为可能危及生命的严重登革热（SD）感染。为了确定SD进展的免疫特征和时间动态，我们通过对从SD进展（SDp）和无并发症登革热(D)患者纵向收集的pbmc进行了深度免疫分析。D的特点是先天免疫应答的早期激活，而SDp的特点是分泌igg的浆细胞和记忆调节性T细胞的快速扩增和激活。同时，SDp，特别是儿童，表现出促炎NK细胞增加，CD16+单核细胞扩增不足，骨髓细胞上FcγR CD64高表达，但抗原呈递减少。综合征特异性决定因素包括休克/出血时树突状细胞丰度受到抑制，器官损伤时浆细胞扩增增强。这项研究揭示了SDp的不协调免疫反应，为人类SD的发病机制提供了新的见解，并为预测和治疗提供了潜在的意义。严重登革热与先天和适应性免疫激活和免疫调节的时间开关失调有关。
Approximately 5 million dengue virus–infected patients progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the FcγR CD64 on myeloid cells, yet a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment. Severe dengue is associated with dysregulated temporal switch of innate and adaptive immune activation and immune regulation.
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影响因子：
46.9
作者：
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通讯作者：
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影响因子：
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影响因子：
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