Li Yiran, Aoki Takahiro, Iwabuchi Sadahiro, Arai Satoshi, Iwabuchi Noriyuki, Motobayashi Hideki, Tanaka Miyuki, Hashimoto Shinichi
Innovative Research Institute, R&D Division, Morinaga Milk Industry Co., Ltd. Zama Kanagawa Japan.
Department of Molecular Pathophysiology Wakayama Medical University Wakayama Wakayama Japan.
Food Sci Nutr. 2024 Feb 7;12(5):3452-3460. doi: 10.1002/fsn3.4009. eCollection 2024 May.
Probiotics are widely used in food for their health benefits to the host. Inactivated probiotics also reportedly improve the intestinal environment and immune regulation. Our previous studies showed that heat-killed MCC1849 (hk-MCC1849) effectively induced IL-12 production in mouse spleen cells and significantly reduced cold symptoms in clinical trial subjects. To further elucidate the mechanism of host immune regulation by hk-MCC1849, human peripheral blood mononuclear cells (PBMCs) were cocultured with hk-MCC1849. The Toll-like receptor 9 ligands CpG-ODN 2216 and hk-MCC1849 and the heat-killed ATCC53103 were used as positive and negative controls, respectively. The results showed that, compared with the control, hk-MCC1849 significantly increased the expression of the plasmacytoid dendritic cell (pDC) marker CD86 ( < .0001) and the pDC marker HLA-DR ( < .001) in PBMCs. The expression levels of the , , , , and genes were significantly increased after coculture with hk-MCC1849 ( < .05, < .05, < .05, < .05, and < .05, respectively, vs. control). Furthermore, to confirm whether hk-MCC1849 directly interacted with pDCs, DCs were enriched with PBMCs following 24 h of coculture with hk-MCC1849. Phagocytosis of fluorescently labeled hk-MCC1849 by pDCs was observed, and there were significant increases in CD86 ( < .05) and HLA-DR ( < .0001) expression in pDCs. These results suggest that hk-MCC1849 exerts a potential immunomodulatory effect on the host through the activation of peripheral pDCs.
益生菌因其对宿主的健康益处而被广泛应用于食品中。据报道,灭活的益生菌也能改善肠道环境并调节免疫。我们之前的研究表明,热灭活的MCC1849(hk-MCC1849)能有效诱导小鼠脾细胞产生白细胞介素-12,并在临床试验受试者中显著减轻感冒症状。为了进一步阐明hk-MCC1849对宿主免疫调节的机制,将人外周血单个核细胞(PBMCs)与hk-MCC1849共培养。分别使用Toll样受体9配体CpG-ODN 2216和hk-MCC1849以及热灭活的ATCC53103作为阳性和阴性对照。结果显示,与对照组相比,hk-MCC1849显著增加了PBMCs中浆细胞样树突状细胞(pDC)标志物CD86(P <.0001)和pDC标志物HLA-DR(P <.001)的表达。与hk-MCC1849共培养后,IL-1β、IL-6、TNF-α、IFN-γ和IL-12基因的表达水平显著升高(分别与对照组相比,P <.05、P <.05、P <.05、P <.05和P <.05)。此外,为了确认hk-MCC1849是否直接与pDC相互作用,在与hk-MCC1849共培养24小时后,用PBMCs富集DCs。观察到pDC对荧光标记的hk-MCC1849的吞噬作用,并且pDC中CD86(P <.05)和HLA-DR(P <.0001)的表达显著增加。这些结果表明,hk-MCC1849通过激活外周pDC对宿主发挥潜在的免疫调节作用。