Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers.
Lactobacillus reuteri-derived extracellular vesicles maintain intestinal immune homeostasis against lipopolysaccharide-induced inflammatory responses in broilers.
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罗伊氏乳杆菌来源的细胞外囊泡维持肠道免疫稳态，对抗脂多糖诱导的肉鸡炎症反应
DOI：
10.1186/s40104-020-00532-4
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发表时间：
2021-02-17
影响因子：
7
通讯作者：
Yang M
中科院分区：
文献类型：
--
作者：
Hu R;Lin H;Wang M;Zhao Y;Liu H;Min Y;Yang X;Gao Y;Yang M
罗伊氏乳杆菌菌株被广泛用作益生菌，通过调节宿主的免疫系统来预防和治疗炎症性肠病。然而，它们与宿主沟通的基本机制还没有被清楚地理解。细菌细胞外囊泡（EV）被认为是宿主-病原体相互作用的重要介质，但其在宿主-病原体相互作用中的潜在作用尚未得到广泛研究。在这里，我们调查了L。reuteri BBC 3，一种乌骨鸡肠道相关的肠道细菌，在鸡模型中使用体内和体外实验在脂多糖（LPS）诱导的肠道炎症的发展中。L. reuteri BBC 3产生尺寸范围为60-250 nm的纳米级膜囊泡。生化和蛋白质组学分析表明，L。罗伊氏BBC 3衍生的EV（LrEV）携带DNA、RNA和先前描述为其他益生菌有益作用的介体的几种生物活性蛋白，例如葡糖基转移酶、丝氨酸蛋白酶和延伸因子Tu。肉鸡体内试验表明，LrEV的施用产生了与L. reuteri BBC 3通过改善生长性能、降低死亡率和减少肠损伤来减轻LPS诱导的炎症。LrEVs可抑制LPS诱导的空肠促炎基因（TNF-α、IL-1β、IL-6、IL-17和IL-8）的表达，提高抗炎基因（IL-10和TGF-β）的表达。LrEV可被鸡巨噬细胞内化。LrEVs体外预处理可通过抑制NF-κB活性降低TNF-α、IL-1β和IL-6的基因表达，增强IL-10和TGF-β的基因表达。此外，LrEVs还可通过激活巨噬细胞，抑制Th 1和Th 17介导的炎症反应，增强免疫调节细胞介导的免疫抑制作用。最后，我们揭示了囊泡蛋白和核酸含量的减少减弱了LrEV对LPS诱导的炎症反应的抑制，表明它们对于LrEV介导的免疫调节是必不可少的。我们发现，LrEVs参与维持肠道免疫稳态对LPS诱导的炎症反应在鸡模型。我们的研究结果提供了机制的洞察力，如何益生菌乳酸菌物种调节宿主的免疫系统在病原体诱导的炎症。在线版本包含补充材料，可通过10.1186/s40104-020-00532-4获得。
Lactobacillus reuteri strains are widely used as probiotics to prevent and treat inflammatory bowel disease by modulating the host’s immune system. However, the underlying mechanisms by which they communicate with the host have not been clearly understood. Bacterial extracellular vesicles (EVs) have been considered as important mediators of host-pathogen interactions, but their potential role in commensals-host crosstalk has not been widely studied. Here, we investigated the regulatory actions of EVs produced by L. reuteri BBC3, a gut-associated commensal bacterium of Black-Bone chicken, in the development of lipopolysaccharide (LPS)-induced intestinal inflammation in a chicken model using both in vivo and in vitro experiments. L. reuteri BBC3 produced nano-scale membrane vesicles with the size range of 60–250 nm. Biochemical and proteomic analyses showed that L. reuteri BBC3-derived EVs (LrEVs) carried DNA, RNA and several bioactive proteins previously described as mediators of other probiotics’ beneficial effects such as glucosyltransferase, serine protease and elongation factor Tu. In vivo broiler experiments showed that administration of LrEVs exerted similar effects as L. reuteri BBC3 in attenuating LPS-induced inflammation by improving growth performance, reducing mortality and decreasing intestinal injury. LrEVs suppressed the LPS-induced expression of pro-inflammatory genes (TNF-α, IL-1β, IL-6, IL-17 and IL-8), and improved the expression of anti-inflammatory genes (IL-10 and TGF-β) in the jejunum. LrEVs could be internalized by chicken macrophages. In vitro pretreatment with LrEVs reduced the gene expression of TNF-α, IL-1β and IL-6 by suppressing the NF-κB activity, and enhanced the gene expression of IL-10 and TGF-β in LPS-activated chicken macrophages. Additionally, LrEVs could inhibit Th1- and Th17-mediated inflammatory responses and enhance the immunoregulatory cells-mediated immunosuppression in splenic lymphocytes of LPS-challenged chickens through the activation of macrophages. Finally, we revealed that the reduced content of both vesicular proteins and nucleic acids attenuated the suppression of LrEVs on LPS-induced inflammatory responses in ex vivo experiments, suggesting that they are essential for the LrEVs-mediated immunoregulation. We revealed that LrEVs participated in maintaining intestinal immune homeostasis against LPS-induced inflammatory responses in a chicken model. Our findings provide mechanistic insight into how commensal and probiotic Lactobacillus species modulate the host’s immune system in pathogens-induced inflammation. The online version contains supplementary material available at 10.1186/s40104-020-00532-4.
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DOI：
10.1038/nrmicro3480
发表时间：
2015-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Brown L;Wolf JM;Prados-Rosales R;Casadevall A
通讯作者：
Casadevall A
影响因子：
4.4
作者：
Christensen, HR;Frokiær, H;Pestka, JJ
通讯作者：
Pestka, JJ
影响因子：
4.6
作者：
Forsberg, Manuel Mata;Bjorkander, Sophia;Sverremark-Ekstrom, Eva
通讯作者：
Sverremark-Ekstrom, Eva
影响因子：
4.8
作者：
Guijarro-Munoz, Irene;Compte, Marta;Sanz, Laura
通讯作者：
Sanz, Laura
影响因子：
3.6
作者：
Chen, Yueping;Zhang, Hao;Zhou, Yanmin
通讯作者：
Zhou, Yanmin