Neff C Preston, Rhodes Matthew E, Arnolds Kathleen L, Collins Colm B, Donnelly Jody, Nusbacher Nichole, Jedlicka Paul, Schneider Jennifer M, McCarter Martin D, Shaffer Michael, Mazmanian Sarkis K, Palmer Brent E, Lozupone Catherine A
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Cell Host Microbe. 2016 Oct 12;20(4):535-547. doi: 10.1016/j.chom.2016.09.002. Epub 2016 Sep 29.
Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties.
两性离子荚膜多糖（ZPSs）是细菌产物，可调节T细胞，包括诱导分泌抗炎性白细胞介素-10的调节性T细胞（Tregs）。然而，已知只有少数几种不同的细菌通过ZPS调节宿主免疫系统。我们展示了一个针对编码ZPS分子的细菌的基因组筛选。我们鉴定出多种与宿主相关的细菌，包括具有已知抗炎特性的共生菌和病原体，它们有能力产生ZPSs。与来自不编码ZPS的亲缘菌株或其中一个假定的ZPS生物合成操纵子被基因破坏的解纤维素拟杆菌共生菌株的裂解物相比，用假定产生ZPS的细菌的裂解物刺激的人单核细胞诱导产生的白细胞介素-10显著更多，且Tregs比例更高。同样，野生型解纤维素拟杆菌DSM 14838可减轻小鼠实验性结肠炎，但缺乏假定ZPS的近缘菌株则不能。总的来说，这个筛选鉴定出了可能利用ZPS与宿主相互作用的细菌菌株以及具有潜在益生菌特性的菌株。
