Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2.
Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2.
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DOI：
10.1002/cti2.1213
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发表时间：
2020
影响因子：
5.8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Jia L;Wu R;Han N;Fu J;Luo Z;Guo L;Su Y;Du J;Liu Y
CD 4 + T细胞是许多由微生物疾病介导的免疫炎症性疾病，特别是炎症性肠病（IBD）的关键。本研究的目的是探讨病原菌和益生菌如何直接影响CD 4 + T细胞中辅助性T细胞（Th）17和调节性T细胞（Treg）平衡来调节炎症。 牙龈卟啉单胞菌（Pg; ATCC 33277）和鼠李糖乳杆菌GG（LGG; CICC 6141）分别被选为代表性病原菌和益生菌。通过超声波和超离心获得细菌提取物。使用流式细胞术、RT-qPCR、ELISA、免疫荧光和Quantibody细胞因子阵列。选择葡聚糖硫酸钠（DSS）诱导的结肠炎模型进行验证。Pg超声处理诱导CD 4 + T细胞凋亡，上调Th 17相关转录因子RoRγt的表达和促炎细胞因子IL-17和IL-6的产生，但下调必需Treg转录因子Foxp 3的表达和抗炎因子TGF-β和IL-10的产生。然而，LGG提取物通过TLR 2途径降低IL-17+ Th 17比例和增加CD 25 + Foxp 3 + Treg比例来维持Th 17/Treg稳态。在体内，Pg刺激的CD 4 + T细胞通过增加结肠和固有层淋巴细胞（LPL）中的Th 17/Treg比率加重DSS诱导的结肠炎，Pg + LGG刺激的CD 4 + T细胞通过JAK-STAT信号通路降低Th 17/Treg比率缓解结肠炎。我们的研究结果表明，致病性Pg和益生菌LGG可以通过不同的TLR直接调节Th 17/Treg平衡。在这项研究中，我们发现致病性牙龈卟啉单胞菌提取物通过TLR 4介导的途径上调了CD 4 + T细胞表面的Th 17/Treg比率，而益生菌鼠李糖乳杆菌GG提取物通过TLR 2途径维持了Th 17/Treg稳态。
CD4+ T cells are the key to many immune–inflammatory diseases mediated by microbial disorders, especially inflammatory bowel disease (IBD). The purpose of this study was to explore how pathogenic and probiotic bacteria directly affect the T helper (Th)17 and T regulatory (Treg) cell balance among CD4+ T cells to regulate inflammation. Porphyromonas gingivalis (Pg; ATCC 33277) and Lactobacillus rhamnosus GG (LGG; CICC 6141) were selected as representative pathogenic and probiotic bacteria, respectively. Bacterial extracts were obtained via ultrasonication and ultracentrifugation. Flow cytometry, RT‐qPCR, ELISAs, immunofluorescence and a Quantibody cytokine array were used. The dextran sodium sulphate (DSS)‐induced colitis model was selected for verification. The Pg ultrasonicate induced the apoptosis of CD4+ T cells and upregulated the expression of the Th17‐associated transcription factor RoRγt and the production of the proinflammatory cytokines IL‐17 and IL‐6, but downregulated the expression of the essential Treg transcription factor Foxp3 and the production of the anti‐inflammatory factors TGF‐β and IL‐10 via the TLR4 pathway. However, LGG extract maintained Th17/Treg homeostasis by decreasing the IL‐17+ Th17 proportion and increasing the CD25+ Foxp3+ Treg proportion via the TLR2 pathway. In vivo, Pg‐stimulated CD4+ T cells aggravated DSS‐induced colitis by increasing the Th17/Treg ratio in the colon and lamina propria lymphocytes (LPLs), and Pg + LGG‐stimulated CD4+ T cells relieved colitis by decreasing the Th17/Treg ratio via the JAK‐STAT signalling pathway. Our findings suggest that pathogenic Pg and probiotic LGG can directly regulate the Th17/Treg balance via different TLRs. In this study, we found that pathogenic Porphyromonas gingivalis extract upregulated the Th17/Treg ratio via the TLR4‐mediated pathway on the surface of CD4+ T cells, while probiotic Lactobacillus rhamnosus GG extract maintained the Th17/Treg homeostasis via the TLR2 pathway.
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