Neutrophils are the most abundant, phenotypically heterogeneous, and exert detrimental or protective roles during anti-viral response. Dengue virus has been reported to activate neutrophils. However, the effect of the dengue virus on the neutrophil phenotypes, survival, and release of inflammatory secretome is yet to be understood. Herein, we investigated the effect of dengue virus serotype-2 (DV-2) on effector functions of naïve neutrophils and studied the impact of its secretome on different immune cells. We found that DV-2 activates purified human neutrophils and causes a significant shift towards the CD16bright/CD62Ldim subtype in an MOI and time-dependent manner. These phenotypically altered neutrophils show delayed apoptosis through NF-ĸB and PI3K pathways and have decreased phagocytic capacity. Treatment of neutrophils with MPO and PAD4 inhibitor before DV-2 incubation, significantly reduced DV-2-induced dsDNA release, suggesting that MPO and PAD4 were involved at early stages for the neutrophil activation and dsDNA release. We also report that DV-2-stimulated neutrophil secretome had a significant effect on viral infection, platelet activation, and naïve neutrophil survival via binding of TNF-α to TNFR1/2 receptors. Furthermore, incubation of endothelial cells with DV-2-stimulated neutrophil secretome potentially inhibits proliferation and wound healing capacity and induces endothelial cell death which can contribute to endothelial barrier dysfunction. In conclusion, the neutrophil-DV-2 interaction modulates the phenotype of neutrophils and the release of prosurvival and antiviral secretome that may act as a double-edged sword during dengue pathogenesis.Keywords: Apoptosis; Dengue virus; Endothelial dysfunction; NETosis; Neutrophil phenotypes; Platelet activation.

---

 

乐备实是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。