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Science ; 359(6380): 1156-1161, 2018 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-29590047

RESUMEN

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.


Asunto(s)
Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/microbiología , Autoinmunidad/genética , Traslocación Bacteriana , Enterococcus/fisiología , Microbioma Gastrointestinal/fisiología , Predisposición Genética a la Enfermedad , Animales , Antibacterianos/farmacología , Autoanticuerpos/inmunología , Autoinmunidad/inmunología , Vacunas Bacterianas/inmunología , ADN Bacteriano/análisis , Enterococcus/efectos de los fármacos , Enterococcus/inmunología , Hepatocitos/microbiología , Humanos , Hígado/microbiología , Ratones , Linfocitos T/inmunología
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