Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease
Extracellular vesicles produced by the human commensal gut bacterium Bacteroides thetaiotaomicron affect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease
复制标题
人类肠道共生细菌拟杆菌产生的细胞外囊泡以细胞类型特异性方式影响宿主免疫途径，这种方式在炎症性肠病中发生改变
DOI：
10.1101/2021.03.20.436262
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Gul L
中科院分区：
文献类型：
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作者：
Gul L
胃肠道 (GI) 拥有复杂的微生物群落，有助于其体内平衡。微生物组遭到破坏会导致胃肠道相关疾病，包括炎症性肠病 (IBD)，因此识别宿主微生物相互作用对于更好地了解肠道健康至关重要。细菌细胞外囊泡（BEV）释放到肠腔中，可以穿过粘液层并进入底层的免疫细胞。为了研究 BEV 与宿主的相互作用，我们研究了肠道共生细菌 Bacteroides thetaiotaomicron 产生的 BEV 对宿主免疫细胞的影响。单细胞 RNA 测序数据和宿主-微生物蛋白质-蛋白质相互作用网络用于预测 BEV 对树突状细胞、巨噬细胞和单核细胞的影响，重点关注 Toll 样受体 (TLR) 途径。我们确定了每种免疫细胞类型和细胞类型特定过程（包括骨髓细胞分化）中受影响的生物过程。 TLR 通路分析强调，在健康与疾病（溃疡性结肠炎）条件下，BEV 靶点在细胞之间以及相同细胞之间存在差异。这些硅发现在 BEV-单核细胞共培养物中得到验证，证明在 BEV 引发的 NF-kB 激活中需要 TLR4 和 Toll-interleukin-1 受体结构域衔接蛋白 (TIRAP)。这项研究表明，细胞类型和健康状况都会影响 BEV 与宿主的通讯。结果和管道可以促进基于 BEV 的 IBD 治疗。
The gastrointestinal (GI) tract harbours a complex microbial community, which contributes to its homeostasis. A disrupted microbiome can cause GI‐related diseases, including inflammatory bowel disease (IBD), therefore identifying host‐microbe interactions is crucial for better understanding gut health. Bacterial extracellular vesicles (BEVs), released into the gut lumen, can cross the mucus layer and access underlying immune cells. To study BEV‐host interactions, we examined the influence of BEVs generated by the gut commensal bacterium,Bacteroides thetaiotaomicron, on host immune cells. Single‐cell RNA sequencing data and host‐microbe protein‐protein interaction networks were used to predict the effect of BEVs on dendritic cells, macrophages and monocytes focusing on the Toll‐like receptor (TLR) pathway. We identified biological processes affected in each immune cell type and cell‐type specific processes including myeloid cell differentiation. TLR pathway analysis highlighted that BEV targets differ among cells and between the same cells in healthy versus disease (ulcerative colitis) conditions. Thein silicofindings were validated in BEV‐monocyte co‐cultures demonstrating the requirement for TLR4 and Toll‐interleukin‐1 receptor domain‐containing adaptor protein (TIRAP) in BEV‐elicited NF‐kB activation. This study demonstrates that both cell‐type and health status influence BEV‐host communication. The results and the pipeline could facilitate BEV‐based therapies for the treatment of IBD.