Wangbin Ning1, Da Cheng2, Philip H Howe3, Chuanxiu Bian4, Diane L Kamen5, Zhenwu Luo4, Xiaoyu Fu2, Elizabeth Ogunrinde4, Liuqing Yang6, Xu Wang7, Quan-Zhen Li8, Jim Oates9, Weiru Zhang10, David White11, Zhuang Wan4, Gary S Gilkeson12, Wei Jiang13. 1. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB208D, Charleston, SC, 29425, USA; Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan, China. 2. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB208D, Charleston, SC, 29425, USA; Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, China. 3. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, SC, USA. 4. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB208D, Charleston, SC, 29425, USA. 5. Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, 114 Doughty Street, Strom Thurmond Research Building Room 416, Charleston, SC, 29403, USA. 6. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB208D, Charleston, SC, 29425, USA; The Third People's Hospital of Shenzhen, Guangdong, China. 7. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB208D, Charleston, SC, 29425, USA; Department of Urology, Capital Medical University Affiliated XuanWu Hospital, Beijing, China. 8. Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. 9. Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, 114 Doughty Street, Strom Thurmond Research Building Room 416, Charleston, SC, 29403, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA. 10. Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan, China. 11. Department of Otolaryngology, Medical University of South Carolina, Charleston, SC, USA. 12. Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, 114 Doughty Street, Strom Thurmond Research Building Room 416, Charleston, SC, 29403, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA. Electronic address: gilkeson@musc.edu. 13. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB208D, Charleston, SC, 29425, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA; Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. Electronic address: jianw@musc.edu.
Abstract
OBJECTIVES: There is an intricate interplay between the microbiome and the immune response impacting development of normal immunity and autoimmunity. However, we do not fully understand how the microbiome affects production of natural-like and pathogenic autoantibodies. Peptidoglycan (PGN) is a component of the bacterial cell wall which is highly antigenic. PGNs from different bacteria can differ in their immune regulatory activities. METHODS: C57BL/6 and MRL/lpr mice were intraperitoneally injected with saline or PGN from Staphylococcus aureus or Bacillus subtilis. Spleen anti-double-stranded DNA (dsDNA) IgG + B cells were sorted for B-cell receptor sequencing. Serum autoantibody levels and kidney damage were analyzed. Further, the association between plasma S. aureus translocation and systemic lupus erythematosus (SLE) pathogenesis was assessed in women. RESULTS: Administration of B. subtilis PGN induced natural-like anti-dsDNA autoantibodies (e.g., IgM, short lived IgG response, and no tissue damage), whereas S. aureus PGN induced pathogenic anti-dsDNA autoantibodies (e.g., prolonged IgG production, low IgM, autoantibody-mediated kidney damage) in C57BL/6 and/or MRL/lpr mice. However, serum total IgG did not differ. S. aureus PGN induced antibodies with reduced clonality and greater hypermutation of IGHV3-74 in splenic anti-dsDNA IgG + B cells from C57BL/6 mice. Further, S. aureus PGN promoted IgG class switch recombination via toll-like receptor 2. Plasma S. aureus DNA levels were increased in women with SLE versus control women and correlated with levels of lupus-related autoantibodies and renal involvement. CONCLUSIONS: S. aureus PGN induces pathogenic autoantibody production, whereas B. subtilis PGN drives production of natural nonpathogenic autoantibodies. Published by Elsevier Ltd.
OBJECTIVES: There is an intricate interplay between the microbiome and the immune response impacting development of normal immunity and autoimmunity. However, we do not fully understand how the microbiome affects production of natural-like and pathogenic autoantibodies. Peptidoglycan (PGN) is a component of the bacterial cell wall which is highly antigenic. PGNs from different bacteria can differ in their immune regulatory activities. METHODS: C57BL/6 and MRL/lpr mice were intraperitoneally injected with saline or PGN from Staphylococcus aureus or Bacillus subtilis. Spleen anti-double-stranded DNA (dsDNA) IgG + B cells were sorted for B-cell receptor sequencing. Serum autoantibody levels and kidney damage were analyzed. Further, the association between plasma S. aureus translocation and systemic lupus erythematosus (SLE) pathogenesis was assessed in women. RESULTS: Administration of B. subtilis PGN induced natural-like anti-dsDNA autoantibodies (e.g., IgM, short lived IgG response, and no tissue damage), whereas S. aureus PGN induced pathogenic anti-dsDNA autoantibodies (e.g., prolonged IgG production, low IgM, autoantibody-mediated kidney damage) in C57BL/6 and/or MRL/lpr mice. However, serum total IgG did not differ. S. aureus PGN induced antibodies with reduced clonality and greater hypermutation of IGHV3-74 in splenic anti-dsDNA IgG + B cells from C57BL/6 mice. Further, S. aureus PGN promoted IgG class switch recombination via toll-like receptor 2. Plasma S. aureus DNA levels were increased in women with SLE versus control women and correlated with levels of lupus-related autoantibodies and renal involvement. CONCLUSIONS: S. aureus PGN induces pathogenic autoantibody production, whereas B. subtilis PGN drives production of natural nonpathogenic autoantibodies. Published by Elsevier Ltd.
Authors: H Bootsma; P E Spronk; E J Ter Borg; E J Hummel; G de Boer; P C Limburg; C G Kallenberg Journal: Ann Rheum Dis Date: 1997-11 Impact factor: 19.103
Authors: Elizabeth Ogunrinde; Zejun Zhou; Zhenwu Luo; Alexander Alekseyenko; Quan-Zhen Li; Danielle Macedo; Diane L Kamen; Jim C Oates; Gary S Gilkeson; Wei Jiang Journal: Arthritis Rheumatol Date: 2019-09-27 Impact factor: 10.995
Authors: M Shlomchik; M Mascelli; H Shan; M Z Radic; D Pisetsky; A Marshak-Rothstein; M Weigert Journal: J Exp Med Date: 1990-01-01 Impact factor: 14.307