Systemic translocation of Staphylococcus drives autoantibody production in HIV disease

DNA, Bacterial Male 0301 basic medicine Staphylococcus HIV Infections Lymphocyte Activation DNA, Ribosomal Microbial ecology Mice 03 medical and health sciences Influenza, Human Animals Humans Autoantibodies Research QR100-130 Hep G2 Cells Germinal Center Immunity, Innate Up-Regulation 3. Good health Disease Models, Animal Influenza Vaccines Bacterial Translocation Plasma microbial 16S rDNA Single-Cell Analysis
DOI: 10.1186/s40168-019-0646-1 Publication Date: 2019-02-14T15:04:15Z
ABSTRACT
Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction remains unknown. Herein, we show that seasonal influenza vaccination induces production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA)) some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not healthy controls. These autoantibodies were derived from antigen-specific B cells activated "bystander" analyzed by single-cell assay study of purified polyclonal ANAs plasma. To explore generation plasma level microbial products, gene expression profile cells, cell receptor (BCR) repertoires analyzed. We found was associated with increased translocation; patients high had skewed upregulation genes related to innate immune activation response translocation. By analyzing circulating 16S rDNA plasma, relative abundance Staphylococcus be subjects. Finally, injection heat-killed aureus promoted germinal center responses mice, consistent notion is triggered products. Our results showed translocation can promote through enhancing production. It uncovers a potential linking autoimmunity disease provides strong rationale targeting prevent
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