title: Staphylococcus aureus infection induces protein A-mediated immune evasion in humans.
abstract: Staphylococcus aureus bacterial infection commonly results in chronic or recurrent disease, suggesting that humoral memory responses are hampered. Understanding how S. aureus subverts the immune response is critical for the rescue of host natural humoral immunity and vaccine development. S. aureus expresses the virulence factor Protein A (SpA) on all clinical isolates, and SpA has been shown in mice to expand and ablate variable heavy 3 (VH3) idiotype B cells. The effects of SpA during natural infection, however, have not been addressed. Acutely activated B cells, or plasmablasts (PBs), were analyzed to dissect the ongoing immune response to infection through the production of monoclonal antibodies (mAbs). The B cells that were activated by infection had a highly limited response. When screened against multiple S. aureus antigens, only high-affinity binding to SpA was observed. Consistently, PBs underwent affinity maturation, but their B cell receptors demonstrated significant bias toward the VH3 idiotype. These data suggest that the superantigenic activity of SpA leads to immunodominance, limiting host responses to other S. aureus virulence factors that would be necessary for protection and memory formation.
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Noel T
authors.initials: NT
authors.lastname: Pauli
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Hwan Keun
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Falugi
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: John
authors.initials: J
authors.lastname: Dulac
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Carole
authors.initials: C
authors.lastname: Henry Dunand
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Nai-Ying
authors.initials: NY
authors.lastname: Zheng
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Kaval
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Andrews
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeDent
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Frank
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Angella
authors.initials: A
authors.lastname: Charnot-Katsikas
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.affiliation: Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 Committee on Immunology; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research; Department of Microbiology; and Department of Pathology, The University of Chicago, Chicago, IL 60637 wilsonp@uchicago.edu.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013205:Staphylococcal Protein A / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D037521:Virulence Factors / Q000276:immunology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D013205:Staphylococcal Protein A; D037521:Virulence Factors