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Science. 2018 Mar 9;359(6380):1156-1161. doi: 10.1126/science.aar7201.

Translocation of a gut pathobiont drives autoimmunity in mice and humans.

Author information

1
Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
2
Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
3
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
4
Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT, USA.
5
Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale School of Medicine, New Haven, CT, USA.
6
Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA. martin.kriegel@yale.edu.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02394964.

PMID:
29590047
PMCID:
PMC5959731
DOI:
10.1126/science.aar7201
[Indexed for MEDLINE]
Free PMC Article

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