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Title Double-Stranded RNA Derived from Lactic Acid Bacteria Augments Th1 Immunity via Interferon-Β from Human Dendritic Cells |
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Type Poster Presentation |
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Theme Probiotics and Prebiotics: Excellence in Science and Clinical Translation |
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Topic Development of Probiotic and Prebiotic Foods, Medical Foods, Supplements and Drugs |
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Main Author Naho Ikari1 |
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Presenting Author Naho Ikari1 |
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Co-Author Tadaomi Kawashima1 Yoshiro Kubota2 Shinichiro Motohashi3 Naoki Shimojo4 Noriko M Tsuji5 |
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Department / Institution / Country Research & Development Division / Kikkoman Corporation / Japan (日本)1 Department of Surgery / Kikkoman General Hospital / Japan (日本)2 Department of Medical Immunology / Graduate School of Medicine, Chiba University / Japan (日本)3 Department of Pediatrics / Graduate School of Medicine, Chiba University / Japan (日本)4 Biomedical Research Institute / National Institute for Advanced Industrial Science and Technology (AIST) / Japan (日本)5 |
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Background and Rationale Lactic acid bacteria (LAB) are one of the major commensal species of small intestine, and are known to modulate immunity. We previously reported that double-stranded RNA (dsRNA) in LAB triggered interferon-β (IFN-β) production by murine dendritic cells (DCs) via endosomal Toll-like receptor 3, which exerted anti-viral and anti-inflammatory effect. |
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Objectives: Indicates the purpose of the study The objective of the present study was to clarify the molecular mechanisms for immunomodulatory effects of LAB focusing on IL-12 and IFN-β production by human DCs. |
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Methodology: Describe pertinent experimental procedures We isolated naïve CD4+ T cells, BDCA1+ DCs (mDC1) and CD14+ monocytes from PBMCs. Monocyte-derived DCs (moDCs) were prepared by culturing CD14+ monocytes in the presence of IL-4 and GM-CSF. We stimulated these cells with heat-killed LAB and assessed mRNA expression, cytokine production and cell differentiation. |
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Results: Summarize the results of the research The secretion of IL-12 from PBMCs provoked by several strains of LAB was abrogated, when LAB were treated with RNase A to deplete both dsRNA and single-stranded RNA (ssRNA). In most strains of LAB, this inhibitory effect was null when the digestion was restricted to ssRNA. IL-12 secretion from PBMCs induced by a strain of LAB, Pediococcus acidilactici strain K15, was attenuated by the neutralizing IFN-β monoclonal antibody, indicating dsRNA of LAB primarily triggered the IFN-β-IL-12 pathway. These results were completely reproducible with moDCs. Moreover, the induction of IL-12 by K15 from moDC was abolished by the inhibition of endosomal acidification, confirming the critical role of endosomal digestion process of LAB. By using co-culture system of naïve CD4+ T cells and mDC1 from PBMCs, we revealed that mDC1 stimulated with K15 induced IFN-γ-producing T cells. |
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Conclusions: State the main conclusions This study indicates that human DCs activated by LAB enhance Th1 immunity, which depends on IFN-β secretion by DCs in response to bacterial dsRNA. |