Generated by gram-negative bacteria, lipopolysaccharides (LPSs) are one of the most abundant and potent immunomodulatory substances present in the intestinal lumen. Interaction of agonistic LPS with the host myeloid-differentiation-2/Toll-like receptor 4 (MD-2/TLR4) receptor complex results in nuclear factor κB (NF-κB) activation, followed by the robust induction of pro-inflammatory immune responses. Here we have isolated LPS from a common gut commensal, Bacteroides vulgatus mpk (BVMPK), which provides only weak agonistic activity. This weak agonistic activity leads to the amelioration of inflammatory immune responses in a mouse model for experimental colitis, and it was in sharp contrast to strong agonists and antagonists. In this context, the administration of BVMPK LPS into mice with severe intestinal inflammation re-established intestinal immune homeostasis within only 2 weeks, resulting in the clearance of all symptoms of inflammation. These inflammation-reducing properties of weak agonistic LPS are grounded in the induction of a special type of endotoxin tolerance via the MD-2/TLR4 receptor complex axis in intestinal lamina propria CD11c+ cells. Thus, weak agonistic LPS represents a promising agent to treat diseases involving pathological overactivation of the intestinal immune system, e.g., in inflammatory bowel diseases.

中文翻译：

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弱刺激性LPS可恢复肠道免疫稳态。

脂多糖（LPS）由革兰氏阴性细菌产生，是肠腔中存在的最丰富和有效的免疫调节物质之一。激动剂LPS与宿主髓样分化2 / Toll样受体4（MD-2 / TLR4）受体复合物的相互作用导致核因子κB（NF-κB）激活，随后强烈诱导促炎性免疫反应。在这里，我们从常见的肠道肠道细菌Bacteroides vulgatus mpk（BVMPK）中分离了LPS，该LPS仅提供弱的激动活性。这种弱的激动活性导致小鼠实验性结肠炎模型的炎症免疫反应得到改善，并且与强效激动剂和拮抗剂形成鲜明对比。在这种情况下，在患有严重肠道炎症的小鼠中施用BVMPK LPS仅在2周内即可重新建立肠道免疫稳态，从而清除了所有炎症症状。弱激动性LPS的这些减轻炎症的特性基于通过固有固有层CD11c +细胞中的MD-2 / TLR4受体复合物轴诱导特殊类型的内毒素耐受性。因此，弱激动性LPS代表了一种有希望的试剂，用于治疗涉及肠道免疫系统的病理性过度活化的疾病，例如在炎症性肠病中。弱激动性LPS的这些减轻炎症的特性基于通过固有固有层CD11c +细胞中的MD-2 / TLR4受体复合物轴诱导特殊类型的内毒素耐受性。因此，弱激动性LPS代表了用于治疗涉及肠道免疫系统的病理性过度活化的疾病的有前途的药剂，例如在炎症性肠病中。弱激动性LPS的这些减轻炎症的特性基于通过固有固有层CD11c +细胞中的MD-2 / TLR4受体复合物轴诱导特殊类型的内毒素耐受性。因此，弱激动性LPS代表了用于治疗涉及肠道免疫系统的病理性过度活化的疾病的有前途的药剂，例如在炎症性肠病中。