Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity
Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity
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DOI：
10.1038/mi.2017.103
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发表时间：
2018-05-01
影响因子：
8
通讯作者：
Kiyono, Hiroshi
中科院分区：
文献类型：
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作者：
Shibata, Naoko;Kunisawa, Jun;Kiyono, Hiroshi
产碱杆菌是一种机会性共生细菌，存在于肠道相关淋巴组织中，如Peyer‘s Patches(PPS)；然而，它们如何在不引起过度炎症反应的情况下创造和维持自身的动态平衡环境仍不清楚。我们的研究表明，产碱菌衍生的脂多糖是Toll样受体4的弱激动剂，能促进树突状细胞产生IL-6，从而促进IgA的产生。产碱杆菌内毒素的致炎活性弱于大肠杆菌来源的内毒素，因此在体内外不会引起过度的炎症反应。产碱菌脂多糖还表现出佐剂作用，诱导抗原特异性免疫反应，而不产生过度炎症。这些发现揭示了PPS中存在共生细菌介导的动态平衡炎症条件，该条件可以在不引起致病性炎症的情况下产生最佳的IgA诱导，并表明产碱菌脂多糖可能是一种安全而有效的佐剂。
Alcaligenes are opportunistic commensal bacteria that reside in gut-associated lymphoid tissues such as Peyer's patches (PPs); however, how they create andmaintain their homeostatic environment, without inducing an excessive inflammatory response remained unclear. We show here that Alcaligenes-derived lipopolysaccharide (Alcaligenes LPS) acts as a weak agonist of toll-like receptor 4 and promotes IL-6 production from dendritic cells, which consequently enhances IgA production. The inflammatory activity of Alcaligenes LPS was weaker than that of Escherichia coli-derived LPS and therefore no excessive inflammation was induced by Alcaligenes LPS in vitro or in vivo. Alcaligenes LPS also showed adjuvanticity, inducing antigen-specific immune responses without excessive inflammation. These findings reveal the presence of commensal bacteria-mediated homeostatic inflammatory conditions within PPs that produce optimal IgA induction without causing pathogenic inflammation and suggest that Alcaligenes LPS could be a safe and potent adjuvant.