Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection.

Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection.
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DOI:
10.1016/j.cell.2019.09.028
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发表时间:
2019-10-17
期刊:
影响因子:
64.5
通讯作者:
Gewirtz AT
Gewirtz AT
中科院分区:
生物学1区
文献类型:
--
作者:
Shi Z;Zou J;Zhang Z;Zhao X;Noriega J;Zhang B;Zhao C;Ingle H;Bittinger K;Mattei LM;Pruijssers AJ;Plemper RK;Nice TJ;Baldridge MT;Dermody TS;Chassaing B;Gewirtz AT

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轮状病毒(RV)在不同的微生物群中遇到肠上皮细胞,开启了微生物影响RV感染的可能性。虽然RV清除通常需要适应性免疫,但我们无意中产生了RV抗性免疫缺陷小鼠,我们假设这反映了选择微生物保护RV。因此,这种rv抗性是通过共住房和粪便移植转移的。通过加热,过滤和抗菌剂对rv保护微生物进行询问,然后限制稀释移植到无菌小鼠和微生物组分析。该方法表明,分段丝状细菌(SFB)足以保护小鼠免受RV感染和相关腹泻。这种保护独立于先前定义的rv阻碍因子,包括干扰素、IL-17和IL-22。SFB在回肠的定殖诱导了宿主基因表达的改变,加速了上皮细胞的更新。RV与含sfb的粪便孵育可降低体外感染性,提示RV可直接中和。因此,SFB不依赖于免疫细胞,对某些肠道病毒感染和相关腹泻疾病具有保护作用。抽象的图。GSU Rag1-KO小鼠微生物群对成年小鼠急性RV感染有保护作用,对成年小鼠慢性RV感染有治疗作用,对新生小鼠RV诱导的腹泻有保护作用。抗病毒活性不仅限于RV,而且对其他病毒有效,包括体内的呼肠孤病毒和体外的IAV和VSV。16S测序产生了一种新的SFB菌株,命名为SFB- g,并且SFB- g单相关粪便样品在赋予GF受体小鼠rv抗性方面与GSU Rag1-KO小鼠微生物群相当。从GSU Rag1-KO小鼠微生物群中分离的SFB-G可诱导肠上皮增殖,并对免疫正常和免疫功能低下的小鼠具有抗rv活性。
Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. While RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immune-deficient mice, which we hypothesized reflected select microbes protecting against RV. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. RV-protecting microbiotas were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) was sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously-defined RV-impeding factors including interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease. Abstract figure. GSU Rag1-KO mice microbiota protect against acute RV infection and cure chronic RV infection in adult mice and protect neonatal mice from RV-induced diarrhea. The antiviral activity is not confined to RV but is effective against other viruses, including reovirus in vivo and IAV and VSV in vitro. 16S sequencing yielded a new strain of SFB, named SFB-G, and SFB-G mono-associated fecal samples are comparable to GSU Rag1-KO mice microbiota in conferring RV-resistance to GF recipient mice. SFB-G isolated from GSU Rag1-KO mice microbiota, induces intestinal epithelium proliferation and confers anti-RV activity to both immunocompetent and immunocompromised mice.
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