Laboratory for Diagnostics of Zoonoses and World Health Organisation (WHO) Center, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Laboratory for Cellular Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Front Immunol. 2023 May 16;14:1190803. doi: 10.3389/fimmu.2023.1190803. eCollection 2023.
Tick-borne encephalitis (TBE) is a viral infection of the human central nervous system caused by the TBE virus (TBEV). The most effective protective measure against TBE is vaccination. Despite the highly immunogenic vaccine, cases of vaccine breakthroughs (VBTs) occur. One of the first targets of infection is dendritic cells (DC), which represent a fundamental bridge between innate and adaptive immunity through antigen presentation, costimulation, and cytokine production. Therefore, we investigated the activation and maturation of DCs and cytokine production after TBEV stimulation of peripheral blood mononuclear cells (PBMCs) obtained from VBT and unvaccinated TBE patients. Our results showed that the expression of HLA-DR and CD86 on DCs, was upregulated to a similar extent in both vaccinated and unvaccinated TBE patients but differed in cytokine production after stimulation with TBEV. PBMCs from patients with VBT TBE responded with lower levels of IFN-α and the proinflammatory cytokines IL-12 (p70) and IL-15 after 24- and 48-hour stimulation with TBEV, possibly facilitating viral replication and influencing the development of cell-mediated immunity. On the other hand, significantly higher levels of IL-6 in addition to an observed trend of higher expression of TNF-α measured after 6 days of stimulation of PBMC could support disruption of the blood-brain barrier and promote viral and immune cell influx into the CNS, leading to more severe disease in VBT TBE patients.
蜱传脑炎（TBE）是一种由 TBE 病毒（TBEV）引起的人类中枢神经系统病毒感染。预防 TBE 最有效的措施是接种疫苗。尽管疫苗具有高度免疫原性，但仍会发生疫苗突破（VBT）病例。感染的第一个靶标之一是树突状细胞（DC），它通过抗原呈递、共刺激和细胞因子产生，代表着先天免疫和适应性免疫之间的基本桥梁。因此，我们研究了 VBT 和未接种 TBE 患者的外周血单核细胞（PBMC）中 TBEV 刺激后 DC 的激活和成熟以及细胞因子的产生。我们的结果表明，接种疫苗和未接种疫苗的 TBE 患者的 DC 上 HLA-DR 和 CD86 的表达上调程度相似，但在 TBEV 刺激后细胞因子的产生上存在差异。VBT TBE 患者的 PBMC 在 24 小时和 48 小时刺激 TBEV 后，IFN-α 和促炎细胞因子 IL-12（p70）和 IL-15 的水平较低，可能促进病毒复制并影响细胞介导的免疫的发展。另一方面，与观察到的 TNF-α表达趋势相比，刺激 PBMC 6 天后，IL-6 的水平显著升高，这可能支持血脑屏障的破坏，并促进病毒和免疫细胞进入中枢神经系统，导致 VBT TBE 患者的病情更严重。
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