肠道致病菌的易位可引发自身免疫病

Title：
Translocation of a gut pathobiont drives autoimmunity in mice and humans

DOI：
10.1126/science.aar7201

Abstract：
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 T cells. 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.

All Authors：
S Manfredo Vieira, M Hiltensperger, V Kumar, D Zegarra-Ruiz, C Dehner, N Khan, F R C Costa, E Tiniakou, T Greiling, W Ruff, A Barbieri, C Kriegel, S S Mehta, J R Knight, D Jain, A L Goodman, M A Kriegel

First Authors：
S Manfredo Vieira

Correspondence：
M A Kriegel

摘要：

     在单一定殖鹑鸡肠球菌（一种肠道致病共生菌）的小鼠及自身免疫易感小鼠模型中，鹑鸡肠球菌易位至肝脏及其它组织中，可诱导自身抗体产生并造成小鼠死亡；通过 抗生素处理可抑制组织中鹑鸡肠球菌的生长、清除致病性自身抗体及T细胞，进而降低小鼠的死亡率； 另外，从自身免疫病患者的肝脏组织中获得鹑鸡肠球菌的特定DNA，制成靶向疫苗并进行肌肉注射，可抑制小鼠的死亡；小鼠及人的肝细胞与鹑鸡肠球菌共同培养，可诱导自身免疫促进因子的产生。