HCMVpp65 422-439 immunization induces lupus-like activity in NZB/W F1 mice We investigated the dynamics of the fecal microbiota associated with lupus-like effects in HCMVpp65 422-439-immunized mice, compared with mice treated with PBS or adjuvant only. In this study, we used HCMVpp65 peptide to immunize NZB/W F1 mice to induce lupus-like effects. Anti-dsDNA antibody production, proteinuria, and glomerular attack have been reported in mice that received CMVpp65 or its fragment 18, 20. Human cytomegalovirus (HCMV), a virus linked to the development of SLE in humans, accelerates lupus-like disease in murine models 18, 19. Pattern changes in intestinal microorganisms or the presence of specific bacterial genera in the gut are associated with immune responses related to lupus. The interplay between dietary tryptophan intake and microbial dysbiosis in lupus-susceptible mice could contribute to the exacerbation of lupus 17. Increased relative abundances of Lachnospiraceae and Rikenellaceae were reported to be associated with the severity of murine lupus, suggesting that the gut microbiota significantly influences the host immune system and effectively affects the development of SLE 15, 16. In animal studies, altered microbial community structure and greater bacterial diversity have been reported in SLE 13, 14. Other human evidence also links gut microbiota changes to the presence of serum antinuclear antibodies and changes in inflammatory cytokines associated with SLE progression 11, 12. Therefore, autoimmune diseases such as SLE may be associated with changes in the gut microbiota.Ī recent cross-sectional study confirmed decreases in species richness diversity and taxonomic complexity in the feces of lupus nephritis patients compared with controls 10. The reciprocal interplay between the intestinal microbiota and the host immune system maintains tissue homeostasis 7, 8, 9.
The mammalian gut is colonized by trillions of microorganisms that shape intestinal microbial diversity, collectively known as the microbiota 6. Although the etiology is uncertain, genetic, environmental, hormonal, and epigenetic factors are associated with SLE development 3, 4, 5. It also results in dysregulation of cytokines, leading to severe and irreversible tissue injury 1, 2. Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune diseases characterized by persistent chronic inflammation and production of autoantibodies, particularly anti-dsDNA antibodies.
This study provides insight into the changes in the gut microbiota after lupus onset in a murine model. Significant correlations between increased abundances of related genera ( Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) and HCMVpp65 peptide immunization-induced lupus-like effects were observed. Statistical analysis of metagenomic profiles showed a higher abundance of various families ( Saccharimonadaceae, Marinifiaceae, and Desulfovibrionaceae) and genera ( Candidatus Saccharimonas, Roseburia, Odoribacter, and Desulfovibrio) in HCMVpp65 peptide-treated mice. The Simpson diversity value was higher in mice injected with HCMVpp65 peptide, but there was no difference in ACE or Chao1 among the three groups. HCMVpp65 peptide immunization induced lupus-like effects, with higher levels of anti-dsDNA antibodies, creatinine, proteinuria, and glomerular damage, compared with mice treated with nothing or adjuvant only. Feces were collected before and after lupus induction biweekly for 16S rRNA sequencing. Three treatment arms for the animals were prepared: intraperitoneal injection of HCMVpp65 peptide, adjuvant alone, and PBS injection. We investigated alterations in the gut microbiota after induction of lupus in a murine model using viral peptide of human cytomegalovirus (HCMV). The association between the gut microbiota and the development of lupus is unclear.