Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
Front Immunol. 2019 Jan 11;9:3007. doi: 10.3389/fimmu.2018.03007. eCollection 2018.
The involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotypic and functional responses of neutrophils in a cohort of adult dengue patients. Results indicated that during an acute DENV infection, neutrophils up-regulate CD66b expression, and produce a more robust respiratory response as compared with that in convalescent or healthy individuals; this confirmed neutrophil activation during DENV infection. Spontaneous decondensation of nuclei, an early event of neutrophil extracellular trap (NET) formation, was also markedly increased in cells isolated from DENV-infected patients during the acute phase of the infection. incubation of NETs with DENV-2 virus significantly decreased DENV infectivity. Interestingly, increased levels of NET components were found in the serum of patients with more severe disease form-dengue hemorrhagic fever (DHF), but not uncomplicated dengue fever, during the acute phase of the infection. Levels of pro-inflammatory cytokines IL-8 and TNFα were also increased in DHF patients as compared with those in healthy and DF subjects. This suggested that NETs may play dual roles during DENV infection. The increased ability for NET formation during acute DENV infection appeared to be independent of PAD4-mediated histone H3 hyper-citrullination. Our study suggests that neutrophils are involved in immunological responses to DENV infection.
免疫系统在保护和引发自然登革热病毒（DENV）感染方面的作用已被广泛研究。然而，尽管有研究提到了 DENV 感染时中性粒细胞的激活，但中性粒细胞的确切作用仍不清楚。在这里，我们研究了一组成年登革热患者中性粒细胞的表型和功能反应。结果表明，在急性 DENV 感染期间，中性粒细胞上调 CD66b 的表达，并产生比恢复期或健康个体更强的呼吸反应；这证实了 DENV 感染期间中性粒细胞的激活。中性粒细胞胞外诱捕网（NET）形成的早期事件，即细胞核自发去凝聚，在感染期急性阶段从 DENV 感染患者中分离的细胞中也明显增加。NET 与 DENV-2 病毒孵育可显著降低 DENV 的感染性。有趣的是，在感染的急性期，病情更严重的登革出血热（DHF）患者的血清中发现 NET 成分水平升高，但无并发症的登革热患者没有升高。促炎细胞因子 IL-8 和 TNFα 的水平在 DHF 患者中也比健康个体和 DF 患者升高。这表明 NET 可能在 DENV 感染中发挥双重作用。在急性 DENV 感染期间，形成 NET 的能力增加似乎与 PAD4 介导的组蛋白 H3 瓜氨酸化无关。我们的研究表明，中性粒细胞参与了对 DENV 感染的免疫反应。
