Translocation of a gut pathobiont drives autoimmunity in mice and humans.
Translocation of a gut pathobiont drives autoimmunity in mice and humans.
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DOI：
10.1126/science.aar7201
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发表时间：
2018-03-09
期刊：
影响因子：
--
通讯作者：
Kriegel MA
中科院分区：
文献类型：
--
作者：
Manfredo Vieira S;Hiltensperger M;Kumar V;Zegarra-Ruiz D;Dehner C;Khan N;Costa FRC;Tiniakou E;Greiling T;Ruff W;Barbieri A;Kriegel C;Mehta SS;Knight JR;Jain D;Goodman AL;Kriegel MA
尽管微生物群与免疫疾病之间存在多种关联，但它们在自身免疫中的作用仍知之甚少。我们发现肠道致病菌，鸡肠球菌，易位到肝脏和其他全身组织触发自身免疫反应的遗传背景下诱发自身免疫。抗生素治疗可防止该模型的死亡率，抑制E.组织中的鸡球虫，并消除致病性自身抗体和T细胞。肝细胞-E.鸡共培养物诱导自身免疫促进因子。单克隆和自身免疫易感小鼠中的病原体易位诱导自身抗体并导致死亡，这可以通过针对病原体的肌内疫苗来预防。E.从自身免疫患者的肝活检中回收了鸡胚特异性DNA，与人肝细胞共培养复制了鼠的发现;因此，在易感人群中明显发生了类似的过程。这些发现表明，肠道致病菌可以在遗传易感宿主中转移并促进自身免疫。
Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and Tcells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.
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影响因子：
3.7
作者：
Furuta Y;Tsai SH;Kinoshita M;Fujimoto K;Okumura R;Umemoto E;Kurashima Y;Kiyono H;Kayama H;Takeda K
通讯作者：
Takeda K
DOI：
10.1038/nrrheum.2012.58
发表时间：
2012-05-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.1222551
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sonnenberg GF;Monticelli LA;Alenghat T;Fung TC;Hutnick NA;Kunisawa J;Shibata N;Grunberg S;Sinha R;Zahm AM;Tardif MR;Sathaliyawala T;Kubota M;Farber DL;Collman RG;Shaked A;Fouser LA;Weiner DB;Tessier PA;Friedman JR;Kiyono H;Bushman FD;Chang KM;Artis D
通讯作者：
Artis D
影响因子：
32.4
作者：
Fung TC;Bessman NJ;Hepworth MR;Kumar N;Shibata N;Kobuley D;Wang K;Ziegler CGK;Goc J;Shima T;Umesaki Y;Sartor RB;Sullivan KV;Lawley TD;Kunisawa J;Kiyono H;Sonnenberg GF
通讯作者：
Sonnenberg GF
影响因子：
56.9
作者：
Spadoni, Ilaria;Zagato, Elena;Rescigno, Maria
通讯作者：
Rescigno, Maria