Translocation of a gut pathobiont drives autoimmunity in mice and humans

By S. Vieira, Michael Hiltensperger, Varun Kumar, Daniel F. Zegarra-Ruiz, C. Dehner, Nafeesa T. Khan, Federico Costa, E. Tiniakou, T. Greiling, W. Ruff and 7 more. Science, 2018

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Bacterial involvement in autoimmunity The composition of the commensal microbiota is known to influence autoimmune disease development and persistence. Manfredo Vieira et al. identified a gut microbe, Enterococcus gallinarum, that translocates from the gut into the organs of mice with a genetic predisposition to lupus-like autoimmunity (see the Perspective by Citi). Molecular signatures of gut barrier disintegration and pathogenic T helper cells were evident in the gut, liver, and lymphoid organs during colonization with the pathobiont. The ensuing pathology could be reversed by vancomycin treatment and by vaccination against E. gallinarum. The same bug was also found in liver biopsies of autoimmune patients, but not in healthy controls. Science, this issue p. 1156; see also p. 1097 Enterococcus gallinarum is implicated in the exacerbation of autoimmune pathology in genetically predisposed mice and humans. 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.

Subfields: Genetics, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/72a2e17901ce11e348c1cc24c84989ca4e7f86f7

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