Systemic translocation of Staphylococcus drives autoantibody production in HIV disease. Microbiome 2019 Feb 14;7(1):25
Date
02/16/2019Pubmed ID
30764863Pubmed Central ID
PMC6376754DOI
10.1186/s40168-019-0646-1Scopus ID
2-s2.0-85061603507 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown.
RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products.
CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.
Author List
Luo Z, Li M, Wu Y, Meng Z, Martin L, Zhang L, Ogunrinde E, Zhou Z, Qin S, Wan Z, Westerink MAJ, Warth S, Liu H, Jin P, Stroncek D, Li QZ, Wang E, Wu X, Heath SL, Li Z, Alekseyenko AV, Jiang WAuthor
Yongxia Wu PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAutoantibodies
Bacterial Translocation
DNA, Bacterial
DNA, Ribosomal
Disease Models, Animal
Germinal Center
HIV Infections
Hep G2 Cells
Humans
Immunity, Innate
Influenza Vaccines
Influenza, Human
Lymphocyte Activation
Male
Mice
Single-Cell Analysis
Staphylococcus
Up-Regulation