Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease
Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease
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DOI：
10.1186/s40168-020-00868-z
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发表时间：
2020-06-08
期刊：
影响因子：
15.5
通讯作者：
Knight, Stella C.
中科院分区：
文献类型：
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作者：
Durant, Lydia;Stentz, Regis;Knight, Stella C.
背景类杆菌是人类肠道微生物区系中的重要成员，与所有革兰氏阴性菌一样，它能自然地产生纳米大小的外膜小泡(OMV)，并从细胞表面萌发出来。重要的是，OMV可以穿过肠道上皮屏障，介导涉及上皮细胞和免疫细胞的微生物-宿主细胞串扰，帮助维持肠道内环境的稳定。在这里，我们研究了Bt OMV与来自健康人和克罗恩病(CD)或溃疡性结肠炎(UC)患者的血液或结肠粘膜来源的树突状细胞(DC)之间的相互作用。结果在健康人中，Bt OMV可刺激结肠DC显著表达IL-10，而在外周血源DC中也可显著刺激IL-6和活化标志物CD80的表达(P分别为0.001和0.01)。相反，在UC，BT OMV不能通过结肠DC诱导IL-10的表达。与对照组相比，UC和CD患者结肠中CD103(+)DC的数量也减少，支持这两种疾病中调节性DC的丢失。此外，在CD和UC中，Bt OMV诱导的DC在血液中表达IL-10的比例显著低于对照组(P<；0.01和P<；0.001)。这些DC对Bt OMV反应的改变在非活动期疾病患者中可见，因此表明炎症性肠病(IBD)对这种共生反应的免疫反应存在内在缺陷。结论总体而言，我们的研究结果表明，在IBD患者健康期间，由共生肠道细菌BT产生的OMV在引导局部和系统对微生物区系成分的平衡免疫反应方面发挥了关键作用。
Background Bacteroides thetaiotaomicron(Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC). Results In healthy individuals, Bt OMVs stimulated significant (p< 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p< 0.001 andp< 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103(+)DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p< 0.01 andp< 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). Conclusions Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients.