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

Autor: E. Scott Helton, Charles O. Elson, Zdenek Hel, Jun Xu, Benjamin S. Christmann, Sonya L. Heath, Jiri Mestecky, E. Turner Overton, Richard P. H. Huijbregts, Warren Denning, Paul A. Goepfert
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
RNA viruses
CD4-Positive T-Lymphocytes
B Cells
Physiology
Chromosomal translocation
HIV Infections
Pathology and Laboratory Medicine
Biochemistry
White Blood Cells
0302 clinical medicine
Immunodeficiency Viruses
Animal Cells
Immune Physiology
Medicine and Health Sciences
030212 general & internal medicine
Intestinal Mucosa
lcsh:QH301-705.5
education.field_of_study
B-Lymphocytes
Immune System Proteins
biology
T Cells
Microbiota
Antibody Isotype Determination
Hematology
3. Good health
Body Fluids
medicine.anatomical_structure
Blood
Medical Microbiology
Viral Pathogens
Viruses
medicine.symptom
Antibody
Cellular Types
Anatomy
Pathogens
Research Article
lcsh:Immunologic diseases. Allergy
T cell
Immune Cells
Population
Immunology
Inflammation
Research and Analysis Methods
Microbiology
Antibodies
Blood Plasma
03 medical and health sciences
Antigen
Antigen Isotypes
Virology
Retroviruses
Genetics
medicine
Humans
Antigens
education
Antibody-Producing Cells
Molecular Biology
Microbial Pathogens
Blood Cells
Lentivirus
Organisms
Biology and Life Sciences
Proteins
HIV
Cell Biology
Immunoglobulin Class Switching
Immunity
Humoral
Immunoglobulin A
B-1 cell
Gastrointestinal Tract
030104 developmental biology
Immunoglobulin class switching
Gene Expression Regulation
lcsh:Biology (General)
Food
Immunoglobulin G
Chronic Disease
biology.protein
HIV-1
Immunologic Techniques
Parasitology
lcsh:RC581-607
Digestive System
Zdroj: PLoS Pathogens, Vol 13, Iss 1, p e1006087 (2017)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: 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.
Author Summary Despite significant effort, our understanding of how HIV-1 virus undermines the immune system is limited. HIV-1infection is characterized by extensive damage to intestinal mucosal barrier and translocation of bacteria and microbial products into the systemic circulation. Immune activation induced by microbial products results in chronic inflammation that drives HIV-1 pathogenesis and progression to AIDS despite successful control of HIV-1 replication by antiretroviral therapy. Here we provide evidence indicating that antibody-producing cells in the intestinal mucosa of HIV-1-infected individuals have decreased capacity to switch from the production of IgM to IgA and IgG, the types of antibodies that normally restrict the translocation of bacterial antigens across the mucosal barrier. This may facilitate systemic dissemination of microbial products and subsequent inflammation in HIV-1-infected individuals. Furthermore, the accumulation of IgM in gut mucosa may contribute to the exacerbation of inflammatory processes by the formation of inflammatory immune complexes. This newly identified dysregulation of immune system alters our understanding of HIV-1 pathogenesis and may facilitate the design of novel therapies targeting immune dysfunction in HIV-1/AIDS.
Databáze: OpenAIRE
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