Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis
Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis
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DOI：
10.1016/j.chom.2019.01.008
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发表时间：
2019-02-13
影响因子：
30.3
通讯作者：
Round, June L.
中科院分区：
文献类型：
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作者：
Gogokhia, Lasha;Buhrke, Kate;Round, June L.
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仍不清楚。我们注意到在实验性治疗细菌驱动的癌症时诱导宿主免疫，这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的免疫细胞扩增。乳酸杆菌、埃希氏菌和拟杆菌噬菌体和噬菌体DNA通过核苷酸敏感受体TLR 9刺激IFN-γ。所产生的免疫应答是噬菌体和细菌特异性的。此外，增加的噬菌体水平通过TLR 9和IFN-γ加重结肠炎。类似地，与无应答者相比，对粪便微生物群移植（FMT）有应答的溃疡性结肠炎（UC）患者具有降低的IFN-γ，并且粘膜IFN-γ与噬菌体水平正相关。与健康个体相比，来自活动性UC患者的噬菌体诱导更多的IFN-γ。总的来说，这些结果表明，噬菌体可以改变粘膜免疫，影响哺乳动物的健康。
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-gamma 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-gamma. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-gamma positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-gamma compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.