title: Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 Infection.
abstract: HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4+ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4+ T cell in HIV-1-infected individuals results in altered humoral responses specific to antigens encountered at mucosal surfaces. Comprehensive protein microarray of systemic humoral responses to intestinal microbiota demonstrated reduced IgG responses to antigens derived from Proteobacteria and Firmicutes but not Bacteroidetes. Importantly, intestinal secretions of antiretroviral therapy-treated HIV-1-infected individuals exhibited a significant elevation of IgM levels and decreased IgA/IgM and IgG/IgM ratios of antibodies specific to a variety of microbial and food antigens. The presented findings indicate reduced competence of mucosal B cells for class switch recombination from IgM to other isotypes limiting their capacity to react to changing antigenic variety in the gut lumen. Decreased availability of microbiota-specific IgA and IgG may be an important factor contributing to the translocation of microbial antigens across the intestinal mucosal barrier and their systemic dissemination that drives chronic inflammation in HIV-1-infected individuals.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.|Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Hel
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Warren L
authors.initials: WL
authors.lastname: Denning
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: E Scott
authors.identifier: 0000-0002-9954-8222
authors.initials: ES
authors.lastname: Helton
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Richard P H
authors.initials: RP
authors.lastname: Huijbregts
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heath
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: E Turner
authors.initials: ET
authors.lastname: Overton
authors.affiliation: Department of Natural Science and Mathematics, Lee University, Cleveland, Tennessee, United States of America.
authors.forename: Benjamin S
authors.identifier: 0000-0002-2478-5581
authors.initials: BS
authors.lastname: Christmann
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.|Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.|Institute of Immunology and Microbiology, 1st School of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Mestecky
mesh_terms: D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D005502:Food; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D064307:Microbiota / Q000276:immunology*
chemical_list: D000941:Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G