The flagellin of candidate live biotherapeutic Enterococcus gallinarum MRx0518 is a potent immunostimulant

被引:47
作者
Laute-Caly, Delphine L. [1 ]
Raftis, Emma J. [1 ]
Cowie, Philip [1 ]
Hennessy, Emma [1 ]
Holt, Amy [1 ]
Panzica, D. Alessio [1 ]
Sparre, Christina [1 ]
Minter, Beverley [1 ]
Stroobach, Eline [1 ]
Mulder, Imke E. [1 ]
机构
[1] 4D Pharma Res Ltd, Life Sci Innovat Bldg,Cornhill Rd, Aberdeen AB25 2ZS, Scotland
基金
英国生物技术与生命科学研究理事会; 英国科研创新办公室;
关键词
INTESTINAL EPITHELIAL-CELLS; TOLL-LIKE RECEPTOR-5; BACTERIAL FLAGELLIN; SEQUENCE DIVERSITY; IL-10; ACTIVATION; PROTEIN; TLR5;
D O I
10.1038/s41598-018-36926-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Many links between gut microbiota and disease development have been established in recent years, with particular bacterial strains emerging as potential therapeutics rather than causative agents. In this study we describe the immunostimulatory properties of Enterococcus gallinarum MRx0518, a candidate live biotherapeutic with proven anti-tumorigenic efficacy. Here we demonstrate that strain MRx0518 elicits a strong pro-inflammatory response in key components of the innate immune system but also in intestinal epithelial cells. Using a flagellin knock-out derivative and purified recombinant protein, MRx0518 flagellin was shown to be a TLR5 and NF-kappa B activator in reporter cells and an inducer of IL-8 production by HT29-MTX cells. E. gallinarum flagellin proteins display a high level of sequence diversity and the flagellin produced by MRx0518 was shown to be more potent than flagellin from E. gallinarum DSM100110. Collectively, these data infer that flagellin may play a role in the therapeutic properties of E. gallinarum MRx0518.
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页数:14
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