Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation.
Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation.
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DOI：
10.1126/sciimmunol.abn6660
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发表时间：
2022-04-08
影响因子：
24.8
通讯作者：
Jeffrey, Kate L.
中科院分区：
文献类型：
--
作者：
Adiliaghdam, Fatemeh;Amatullah, Hajera;Digumarthi, Sreehaas;Saunders, Tahnee L.;Rahman, Raza-Ur;Wong, Lai Ping;Sadreyev, Ruslan;Droit, Lindsay;Paquette, Jean;Goyette, Philippe;Rioux, John D.;Hodin, Richard;Mihindukulasuriya, Kathie A.;Handley, Scott A.;Jeffrey, Kate L.
改变的肠道微生物与宿主遗传学一致形成炎症性肠病（IBD）表型。然而，洞察力仅限于细菌和真菌。我们发现，从非IBD、非炎症的人类结肠切除物中富集的真核病毒和噬菌体（统称为病毒组）积极引发非典型抗炎先天免疫程序。相反，溃疡性结肠炎或克罗恩病结肠切除病毒引起炎症，这是成功地抑制了非IBD病毒。IBD结肠组织病毒组受到干扰，包括肠道病毒B类真核小核糖核酸病毒增加，这在粪便病毒组研究中未检出。用非IBD结肠组织病毒组人源化的小鼠被保护免于肠道炎症，而IBD病毒组小鼠以核酸感测依赖性方式表现出加剧的炎症。此外，当暴露于病毒组时，IBD患者来源的肠上皮细胞在病毒传感器MDA 5内具有功能丧失突变，这会产生有害后果。我们的研究结果表明，先天识别IBD或非IBD人类病毒组自主影响肠道内稳态和疾病表型。因此，肠道病毒组的扰动或由于遗传变异而改变的感知病毒组的能力有助于IBD的诱导。利用病毒组可能提供治疗和生物标志物的潜力。人类肠道病毒不同地塑造宿主免疫和疾病。
Altered enteric microorganisms in concert with host genetics shape inflammatory bowel disease (IBD) phenotypes. However, insight is limited to bacteria and fungi. We found that eukaryotic viruses and bacteriophages (collectively, the virome), enriched from non-IBD, non-inflamed human colon resections, actively elicited atypical anti-inflammatory innate immune programs. Conversely, ulcerative colitis or Crohn’s disease colon resection viromes provoked inflammation, which was successfully dampened by non-IBD viromes. The IBD colon tissue virome was perturbed, including an increase in the Enterovirus B species of eukaryotic picornaviruses, not previously detected in fecal virome studies. Mice humanized with non-IBD colon tissue viromes were protected from intestinal inflammation while IBD-virome mice exhibited exacerbated inflammation in a nucleic acid sensing-dependent fashion. Furthermore, there were detrimental consequences for IBD patient-derived intestinal epithelial cells bearing loss-of-function mutations within virus sensor MDA5 when exposed to viromes. Our results demonstrate that innate recognition of IBD or non-IBD human viromes autonomously influences intestinal homeostasis and disease phenotypes. Thus, perturbations in the intestinal virome, or an altered ability to sense the virome due to genetic variation, contribute to the induction of IBD. Harnessing the virome may offer therapeutic and biomarker potential. Human enteric viromes divergently shape host immunity and disease.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
5.8
作者：
Bichet MC;Chin WH;Richards W;Lin YW;Avellaneda-Franco L;Hernandez CA;Oddo A;Chernyavskiy O;Hilsenstein V;Neild A;Li J;Voelcker NH;Patwa R;Barr JJ
通讯作者：
Barr JJ
DOI：
10.1073/pnas.1305923110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Barr, Jeremy J.;Auro, Rita;Rohwer, Forest
通讯作者：
Rohwer, Forest
影响因子：
28.3
作者：
Edwards, Robert A.;Vega, Alejandro A.;Dutilh, Bas E.
通讯作者：
Dutilh, Bas E.