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Lymphoid tissue-resident Alcaligenes LPS induces IgA production without excessive inflammatory responses via weak TLR4 agonist activity.
Mucosal Immunology ( IF 8 ) Pub Date : 2018-05-01 , DOI: 10.1038/mi.2017.103
Naoko Shibata 1, 2, 3 , Jun Kunisawa 1, 3, 4, 5, 6 , Koji Hosomi 3 , Yukari Fujimoto 7, 8 , Keisuke Mizote 8 , Naohiro Kitayama 8 , Atsushi Shimoyama 8 , Hitomi Mimuro 9, 10 , Shintaro Sato 1, 4, 11 , Natsuko Kishishita 12 , Ken J Ishii 12, 13 , Koichi Fukase 8 , Hiroshi Kiyono 1, 2, 4
Affiliation  

Alcaligenes are opportunistic commensal bacteria that reside in gut-associated lymphoid tissues such as Peyer's patches (PPs); however, how they create and maintain 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.

中文翻译:

驻留在淋巴组织中的产碱菌 LPS 通过弱 TLR4 激动剂活性诱导 IgA 的产生而不会产生过度的炎症反应。

产碱菌是机会性共生细菌,存在于肠道相关淋巴组织中,例如淋巴集结 (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稳态环境仍不清楚。我们在此表明​​,产碱菌衍生的脂多糖 (Alcaligenes LPS) 充当 toll 样受体 4 的弱激动剂,并促进树突状细胞产生 IL-6,从而增强 IgA 的产生。产碱菌 LPS 的炎症活性弱于大肠杆菌来源的 LPS,因此产碱菌 LPS 在体外或体内均未引起过度炎症。Alcaligenes LPS 还显示出佐剂性,可诱导抗原特异性免疫反应而不会引起过度炎症。
更新日期:2018-02-07
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