The gut microbiota from lupus-prone B6. Sle1.Sle2.Sle3 (TC) induces inflammation via a mechanism other than bacterial translocation

Abstract

Abstract The lupus-prone microbiota from TC mice induces autoimmunity when transferred to germ-free B6 mice and broad-spectrum antibiotic treatment attenuates autoimmunity in TC mice, demonstrating a microbiota involvement in inflammation. Aged TC mice show colon inflammation relative to B6 controls Fecal blood was detected in approximately 30% of aged TC mice tested, whereas B6 mice were negative. Based on these findings, we sought to understand if compromised barrier integrity could account for the proinflammatory nature of the TC microbiota. Serum endotoxin and intestinal tight junction protein expression were similar between TC and B6 controls, and serum FITC levels were lower in TC mice following FITC-dextran gavage. Colony growth was found in about 30% of aged TC liver and mesenteric lymph node homogenates, but not in the tissues of pre-autoimmune TC mice. The TC bacterial colonies were identified as Staphylococcus xylosus, a non-pathogenic commensal. These findings suggest that TC mice do not have a compromised intestinal barrier, and that the bacterial translocation that occurs in a minority of TC mice only after the onset of autoimmunity is a consequence, rather than a cause of autoimmunity. Therefore, the inflammatory nature of the TC microbiota is likely related to immune activation starting in the gut itself through the production of specific metabolites.