Spontaneous Translocation of a Gut Pathobiont Drives Autoimmunity that is Preventable by Intramuscular Vaccination

Autor: Silvio Manfredo Vieira, Michael Hiltensperger, Varun Kumar, Carina Dehner, Daniel Zegarra-Ruiz, William Ruff, Nafeesa Khan, Andrew Goodman, Martin A Kriegel
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Immunology. 198:199.20-199.20
ISSN: 1550-6606
0022-1767
Popis: The gut microbiota contributes to the pathogenesis of autoimmunity. The mechanisms and sites of host-microbiota interactions are, however, largely unknown. Dietary antigens reach the mesenteric lymph node (MLN) via the lymphatics and the liver via the portal vein. We hypothesized that commensals reach lymphocytes beyond the gut barrier in autoimmune-prone hosts. We first altered the gut microbiota with single antibiotics in the (NZWxBXSB)F1 model of systemic autoimmunity that is characterized by a leaky barrier based on oral gavage with FITC-dextran. To test commensal translocation, we cultured anaerobically MLN and livers. Compared to controls, vancomycin alone lowered autoantibodies, Th17 and Tfh cells, and protected mice from autoimmune deaths. Cultures of MLN and liver of (NZWxBXSB)F1 mice revealed significant anaerobic growth, which was suppressed by vancomycin. Sequencing of colonies identified E. gallinarum, a human gut commensal, that grew uniquely in tissues of autoimmune but not control mice. Species-specific PCR of liver tissues from autoimmune hepatitis patients also revealed E. gallinarum. 16S rDNA sequencing confirmed the presence of Enterococcus genus in the gut of (NZWxBXSB)F1 mice. Germ-free C57BL/6 mice monocolonized with E. gallinarum also led to translocation and induction of autoantibodies as well as Th1/Th17 responses. Remarkably, an intramuscular vaccine against E. gallinarum prevented autoimmune deaths in (NZWxBXSB)F1 mice. These data support that an innocuous gut commensal translocates spontaneously to initiate autoimmunity that is preventable by a vaccine targeted at the translocating pathobiont. This approach represents a novel therapeutic avenue for immune-mediated diseases.
Databáze: OpenAIRE
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