Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Northeastern Science Inspection Station, China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, Harbin 150030, China.
Cytokine. 2021 Aug;144:155581. doi: 10.1016/j.cyto.2021.155581. Epub 2021 May 22.
Lactobacilli are abundant in the intestinal tract where they constantly regulate immune system via interacting with a great diversity of immune cells, such as dendritic cells (DCs). Notably, DCs are powerful antigen-presenting cells and they are capable of initiating primary immune responses. In this study, we studied the effects of Lactobacillus johnsonii (L. johnsonii) and Lactobacillus johnsonii cell-free supernatant (L. johnsonii-CFS) on the activation of porcine monocyte-derived dendritic cells (MoDCs) and their regulation of Th cellular immune responses in vitro. The MoDCs generated from porcine peripheral blood monocytes were stimulated by L. johnsonii and L. johnsonii-CFS, respectively. Pre-incubation with L. johnsonii increased expression of CD172a, CD80, major histocompatibility complex class II (MHCII) in MoDCs, and enhanced the ability of MoDCs to induce the proliferation of CD4 T cell, while pre-incubation with L. johnsonii-CFS merely upregulated the expression of MHCII. Analysis of the cytokines showed that L. johnsonii stimulated up-regulation of Th1-type cytokines (IL-12p40, IFN-γ, TNF-α), pro-inflammatory cytokine IL-1β, chemokine CCL20, and Treg-type / anti-inflammatory cytokines IL-10 in MoDCs. Notably, a high production of IL-10 was observed in the MoDCs treated with L. johnsonii-CFS, indicating L. johnsonii-CFS exerted anti-inflammatory effects. Furthermore, L. johnsonii induced up-regulation of TLR2 and TLR6, but L. johnsonii-CFS not. Moreover, MoDCs stimulated by L. johnsonii mainly promoted T cell differentiate into Th1/Th2/Treg cells and plays an important role in improving the balance between Th1/Th2/Treg-type cells, whereas MoDCs stimulated by L. johnsonii-CFS mainly directed T cell to Th2/Treg subset polarization. In conclusion, L. johnsonii and L. johnsonii-CFS exhibited the ability of modulating innate immunity by regulating immunological functions of MoDCs in vitro, suggesting their potential ability to use as microecological preparations and medicines.
乳杆菌在肠道中大量存在，通过与多种免疫细胞（如树突状细胞（DCs））相互作用，不断调节免疫系统。值得注意的是，DCs 是强大的抗原呈递细胞，能够启动初级免疫反应。在这项研究中，我们研究了植物乳杆菌（Lactobacillus johnsonii，L. johnsonii）和植物乳杆菌无细胞上清液（L. johnsonii cell-free supernatant，L. johnsonii-CFS）对体外猪单核细胞来源树突状细胞（monocyte-derived dendritic cells，MoDCs）激活及其对 Th 细胞免疫应答的调节作用。从猪外周血单核细胞中生成的 MoDCs 分别受到 L. johnsonii 和 L. johnsonii-CFS 的刺激。L. johnsonii 的预孵育增加了 MoDCs 中 CD172a、CD80、主要组织相容性复合体 II（major histocompatibility complex class II，MHCII）的表达，并增强了 MoDCs 诱导 CD4 T 细胞增殖的能力，而 L. johnsonii-CFS 的预孵育仅上调了 MHCII 的表达。细胞因子分析表明，L. johnsonii 刺激了 Th1 型细胞因子（IL-12p40、IFN-γ、TNF-α）、促炎细胞因子 IL-1β、趋化因子 CCL20 和 Treg 型/抗炎细胞因子 IL-10 在 MoDCs 中的表达上调。值得注意的是，在接受 L. johnsonii-CFS 处理的 MoDCs 中观察到高水平的 IL-10 产生，表明 L. johnsonii-CFS 发挥了抗炎作用。此外，L. johnsonii 诱导了 TLR2 和 TLR6 的上调，但 L. johnsonii-CFS 没有。此外，L. johnsonii 刺激的 MoDCs 主要促进 T 细胞分化为 Th1/Th2/Treg 细胞，并在改善 Th1/Th2/Treg 细胞类型之间的平衡方面发挥重要作用，而 L. johnsonii-CFS 刺激的 MoDCs 主要指导 T 细胞向 Th2/Treg 亚群极化。总之，L. johnsonii 和 L. johnsonii-CFS 通过调节 MoDCs 的免疫功能，表现出调节固有免疫的能力，提示它们作为微生态制剂和药物的潜在应用能力。
