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Microbiome. 2019 Feb 14;7(1):25. doi: 10.1186/s40168-019-0646-1.

Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.

Author information

1
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave. BSB208D, Charleston, SC, 29425, USA.
2
Department of Gastroenterology, Oncology Bioinformatics Center, Minhang Hospital, Fudan University, Shanghai, China.
3
Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.
4
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
5
Cell Processing Section (CPS), Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, 20892, USA.
6
Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
7
Sidra Medical and Research Center, Doha, Qatar.
8
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, 10016, USA.
9
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
10
Program for Human Microbiome Research, Biomedical Informatics Center, Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA.
11
Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave. BSB208D, Charleston, SC, 29425, USA. jianw@musc.edu.
12
Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA. jianw@musc.edu.

Abstract

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.

KEYWORDS:

Autoantibodies; Plasma microbial 16S rDNA; Staphylococcus

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