Research Laboratories for Health Science and Food Technologies, Kirin Company, Ltd., Yokohama‑shi, Kanagawa 236‑0004, Japan.
National Institute of Infectious Diseases, Tokyo 162‑8640, Japan.
Int J Mol Med. 2019 Jan;43(1):426-434. doi: 10.3892/ijmm.2018.3955. Epub 2018 Oct 24.
Dengue virus (DENV), a mosquito‑borne flavivirus, causes an acute febrile illness that is a major public health problem in the tropics and subtropics globally. However, methods to prevent or treat DENV infection have not been well established. It was previously demonstrated that Lactococcus lactis strain plasma (LC‑plasma) has the ability to stimulate plasmacytoid dendritic cells (pDCs). As pDCs are key immune cells that control viral infection by producing large amounts of type I interferons (IFN), the present study evaluated the effect of LC‑plasma on DENV infection using a mouse infectious DENV strain. Mice were divided into two groups and the test group was orally administered LC‑plasma for two weeks. Two weeks following administration, the mice were infected with DENV and the relative viral titers and the expression of the inflammatory genes in DENV‑infected tissue were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The relative viral titers were notably lower in the DENV‑infected tissues compared with the control group when LC‑plasma was orally administered prior to DENV infection. Furthermore, the expression of the inflammatory genes associated with DENV infection was also reduced by LC‑plasma administration. To investigate how LC‑plasma administration controls DENV infection, the present study examined anti‑viral gene expression, which is critical for the viral clearance induced by type I IFN. Two weeks subsequent to the administration of LC‑plasma, the expression of anti‑viral gene was measured using RT‑qPCR. Oral intake of LC‑plasma enhanced anti‑viral gene expression in DENV‑infected spleen tissue. To clarify the detailed mechanism, in vitro co‑culture studies using bone‑marrow derived DC (BMDC) were performed. BMDC were stimulated with LC‑plasma in combination with anti‑IFN‑α/β antibody and the expression of anti‑viral genes was measured. In vitro studies revealed that the effect of LC‑plasma on anti‑viral genes was dependent on type I IFN. Based on these results, LC‑plasma may be effective against DENV infection by stimulating pDCs, which results in the increased production of anti‑viral factors.
登革热病毒（DENV）是一种通过蚊子传播的黄病毒，会引起急性发热疾病，是全球热带和亚热带地区的主要公共卫生问题。然而，目前尚未开发出预防或治疗 DENV 感染的有效方法。先前的研究表明，乳酸乳球菌血浆（LC-血浆）具有刺激浆细胞样树突状细胞（pDC）的能力。由于 pDC 是通过产生大量 I 型干扰素（IFN）来控制病毒感染的关键免疫细胞，因此本研究使用小鼠感染性 DENV 株评估了 LC-血浆对 DENV 感染的影响。将小鼠分为两组，实验组连续两周口服 LC-血浆。给药两周后，用 DENV 感染小鼠，并使用逆转录定量聚合酶链反应（RT-qPCR）测量 DENV 感染组织中的相对病毒滴度和炎症基因的表达。与对照组相比，当在 DENV 感染前口服给予 LC-血浆时，DENV 感染组织中的相对病毒滴度明显较低。此外，LC-血浆给药还降低了与 DENV 感染相关的炎症基因的表达。为了研究 LC-血浆给药如何控制 DENV 感染，本研究检查了抗病毒基因表达，这对于 I 型 IFN 诱导的病毒清除至关重要。在给予 LC-血浆两周后，使用 RT-qPCR 测量抗病毒基因的表达。口服摄入 LC-血浆增强了 DENV 感染脾组织中的抗病毒基因表达。为了阐明详细的机制，进行了使用骨髓来源的树突状细胞（BMDC）的体外共培养研究。用 LC-血浆联合抗 IFN-α/β 抗体刺激 BMDC，并测量抗病毒基因的表达。体外研究表明，LC-血浆对抗病毒基因的作用依赖于 I 型 IFN。基于这些结果，LC-血浆通过刺激 pDC 可能对 DENV 感染有效，从而导致抗病毒因子的产生增加。
