Administration of plasmacytoid dendritic cell-stimulative lactic acid bacteria is effective against dengue virus infection in mice

• Published in: International journal of molecular medicine Vol. 43; no. 1; pp. 426 - 434
• Main Authors: Suzuki, Hiroaki, Tsuji, Ryohei, Sugamata, Miho, Yamamoto, Naoki, Yamamoto, Norio, Kanauchi, Osamu
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.01.2019; Spandidos Publications UK Ltd
• Subjects: Administration, Oral; Animals; Care and treatment; CD11 Antigens - metabolism; Dendritic Cells - immunology; Dengue - microbiology; Dengue - virology; Dengue fever; Dengue Virus - physiology; Female; Gene Expression Regulation; Genetic aspects; Gram-positive bacteria; Inflammation - pathology; Interferon Type I - metabolism; Kinases; Lactobacillales - metabolism; Lactococcus - metabolism; Mice, Inbred C57BL; Rodents; Spleen - pathology; Spleen - virology; Viral infections; Viruses; United States > US; Japan
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2018.3955

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.