Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses
Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses
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DOI：
10.3389/fimmu.2019.03093
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发表时间：
2020-01-24
影响因子：
7.3
通讯作者：
Frick, Julia-Stefanie
中科院分区：
文献类型：
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作者：
Maerz, Jan Kevin;Trostel, Constanze;Frick, Julia-Stefanie
B 细胞具有多方面的功能，可影响健康和疾病期间的免疫反应。在炎症性肠病、多发性硬化症和类风湿性关节炎等自身免疫性疾病中，功能性 B 细胞的耗竭会导致人类和相应小鼠模型的疾病恶化。这可能是由于缺乏关键的 B 细胞亚群：调节性 B 细胞 (Breg)。尽管 Breg 只占所有免疫细胞的一小部分，但它们在调节免疫反应方面表现出关键特性，从而有助于维持健康个体的免疫稳态。在这项研究中，我们报告说 Bregs 的诱导是由宿主微生物群的免疫原性差异触发的。在低免疫原性普通拟杆菌和强免疫原性大肠杆菌的比较实验中，我们发现Bregs的诱导和寿命取决于强免疫原性共生体抗原介导的强Toll样受体激活。大肠杆菌对 B 细胞进行有效刺激，导致 B 细胞表面抑制性分子的显着表达，并增加白细胞介素 10 等抗炎细胞因子的产生。这些细菌引发的 Breg 能够有效抑制树突状细胞 (DC) 的成熟和功能，防止辅助性 T (Th)1 和 Th17 细胞的增殖和极化，同时在体外促进 Th2 细胞分化。此外，Bregs 促进了调节性 T 细胞 (Treg) 的发育，从而可能形成反馈合作以建立免疫稳态。此外，在无菌野生型小鼠中定植大肠杆菌而非普通双歧杆菌，可显着减少葡聚糖硫酸钠（DSS）诱导的结肠炎中的肠道炎症过程，并与免疫抑制性Bregs的诱导增加相关。 Bregs 的数量与炎症的严重程度直接相关。这些发现可能为微生物驱动的自身免疫性疾病的 B 细胞控制治疗提供新的见解和治疗方法。
B cells fulfill multifaceted functions that influence immune responses during health and disease. In autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, depletion of functional B cells results in an aggravation of disease in humans and respective mouse models. This could be due to a lack of a pivotal B cell subpopulation: regulatory B cells (Bregs). Although Bregs represent only a small proportion of all immune cells, they exhibit critical properties in regulating immune responses, thus contributing to the maintenance of immune homeostasis in healthy individuals. In this study, we report that the induction of Bregs is differentially triggered by the immunogenicity of the host microbiota. In comparative experiments with low immunogenic Bacteroides vulgatus and strong immunogenic Escherichia coli, we found that the induction and longevity of Bregs depend on strong Toll-like receptor activation mediated by antigens of strong immunogenic commensals. The potent B cell stimulation via E. coli led to a pronounced expression of suppressive molecules on the B cell surface and an increased production of anti-inflammatory cytokines like interleukin-10. These bacteria-primed Bregs were capable of efficiently inhibiting the maturation and function of dendritic cells (DCs), preventing the proliferation and polarization of T helper (Th)1 and Th17 cells while simultaneously promoting Th2 cell differentiation in vitro. In addition, Bregs facilitated the development of regulatory T cells (Tregs) resulting in a possible feedback cooperation to establish immune homeostasis. Moreover, the colonization of germfree wild type mice with E. coli but not B. vulgatus significantly reduced intestinal inflammatory processes in dextran sulfate sodium (DSS)-induced colitis associated with an increase induction of immune suppressive Bregs. The quantity of Bregs directly correlated with the severity of inflammation. These findings may provide new insights and therapeutic approaches for B cell-controlled treatments of microbiota-driven autoimmune disease.