Patterson Angela M, Mulder Imke E, Travis Anthony J, Lan Annaig, Cerf-Bensussan Nadine, Gaboriau-Routhiau Valerie, Garden Karen, Logan Elizabeth, Delday Margaret I, Coutts Alistair G P, Monnais Edouard, Ferraria Vanessa C, Inoue Ryo, Grant George, Aminov Rustam I
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
INSERM, UMR1163, Lab Intestinal Immunity, Paris, France.
Front Immunol. 2017 Sep 26;8:1166. doi: 10.3389/fimmu.2017.01166. eCollection 2017.
is a flagellated gut anaerobic bacterium belonging to the family within the Firmicutes phylum. A significant decrease of colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of -host cross talk using both murine and models.
The complete genome sequence of A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with , and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed and using the TLR5KO and DSS-colitis murine models.
In the bacterium, , host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4CD25FoxP3 T cell numbers increased in the of both mono-associated and conventional mice treated with . Treatment with the bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated.
Mono-association of mice with bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in , while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of that could be useful for the control and treatment of gut inflammation.
是一种属于厚壁菌门内该科的有鞭毛的肠道厌氧菌。最近已证明溃疡性结肠炎患者肠道中的定殖显著减少。在这项工作中，我们使用小鼠和模型研究了与宿主相互作用的机制。
确定了A2 - 183的完整基因组序列。将C3H/HeN无菌小鼠用单一定殖，并用组织学、转录组分析和流式细胞术研究宿主 - 微生物相互作用。使用TLR5KO和DSS - 结肠炎小鼠模型进行了进一步研究。
在该细菌中，宿主肠道定殖上调了参与接合/移动、代谢、运动性和趋化性的基因。在宿主细胞中，细菌定殖上调了与抗菌肽、肠道屏障功能、Toll样受体（TLR）信号传导和T细胞生物学相关的基因。在用处理的单关联和常规小鼠的中，CD4CD25FoxP3 T细胞数量增加。用该细菌处理可提供针对DSS诱导的结肠炎的保护。还研究了鞭毛蛋白在宿主 - 细菌相互作用中的作用。
小鼠与细菌的单关联导致特定的双向基因表达模式。一组被认为对宿主定殖很重要的基因在中被诱导，而宿主细胞通过加强肠道屏障功能和增强调节性T细胞群体扩增做出反应，可能是通过TLR5 - 鞭毛蛋白信号传导。我们的数据揭示了的免疫调节特性，这可能对肠道炎症的控制和治疗有用。
