Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; Joan and Sanford I. Weill Department of Medicine, Jill Roberts Center and Institute for Research in Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, USA.
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Cell Host Microbe. 2019 Feb 13;25(2):285-299.e8. doi: 10.1016/j.chom.2019.01.008.
Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9. The resultant immune responses were both phage and bacteria specific. Additionally, increasing bacteriophage levels exacerbated colitis via TLR9 and IFN-γ. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-γ positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-γ compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.
噬菌体是微生物群中最丰富的成员，具有塑造肠道细菌群落的潜力。噬菌体组成的变化与疾病有关，但噬菌体如何影响哺乳动物的健康尚不清楚。我们在实验性治疗细菌驱动的癌症时注意到宿主免疫的诱导，这促使我们测试噬菌体是否改变免疫反应。用噬菌体治疗无菌小鼠会导致肠道中免疫细胞的扩张。乳杆菌、大肠杆菌和拟杆菌噬菌体和噬菌体 DNA 通过核苷酸感应受体 TLR9 刺激 IFN-γ。由此产生的免疫反应既具有噬菌体特异性又具有细菌特异性。此外，通过 TLR9 和 IFN-γ，增加噬菌体水平会加剧结肠炎。同样，对粪便微生物群移植 (FMT) 有反应的溃疡性结肠炎 (UC) 患者与无反应者相比，噬菌体水平降低，粘膜 IFN-γ与噬菌体水平呈正相关。来自活动期 UC 患者的噬菌体比健康个体诱导更多的 IFN-γ。总的来说，这些结果表明噬菌体可以改变粘膜免疫，从而影响哺乳动物的健康。
