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Mycobacterium tuberculosis infection boosts B cell responses to unrelated pathogens

Mycobacterium tuberculosis infection boosts B cell responses to unrelated pathogens

来源:bioRxiv_logobioRxiv
英文摘要

Abstract Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.tb infection or whether vaccination with the related species, Mycobacterium bovis BCG, has a similar effect. This study investigated the effects of M.tb infection and BCG vaccination on B cell responses to heterologous pathogen recall antigens. Antibodies against several bacterial and viral pathogens were quantified by ELISA in 68 uninfected controls, 62 individuals with latent TB infection (LTBI) and 107 active pulmonary TB (APTB) cases, and 24 recently BCG-vaccinated adolescents and naive controls. Antibody avidity was investigated using surface plasmon resonance and B cell ELISPOT assays were used to measure plasmablast and memory B cell responses (MBC) in APTB cases and healthy donor controls. APTB was associated with higher levels of antibodies to tetanus toxoid (TT), diphtheria toxoid, respiratory syncytial virus, measles virus and Kaposi’s sarcoma herpesvirus, compared to uninfected controls. Vaccination with BCG did not alter levels of antibodies against heterologous pathogens. TT-specific antibody avidity was increased in APTB and the ratio of TT-specific plasmablasts to MBCs in the APTB cases was 7:1. M.tb infection boosts serological memory to heterologous pathogens in human subjects and this process may be driven by polyclonal activation of memory B cells. SignificanceMycobacterium tuberculosis (M.tb) has potent immunostimulatory properties and has been used in adjuvant preparations to improve vaccine responses in animals. This study shows that natural M.tb infection in humans is associated with increased antibody and B cell recall responses to heterologous pathogens. This data suggests a potential role for M.tb antigens in immunotherapies designed to maintain antibody immunity to diverse infections.

Kimuda Simon G.、Andia-Biraro Irene、Sebina Ismail、Egesa Moses、Smith Steven G.、Nalwoga Angela、Raynes John G.、Levin Jonathan、Cose Stephen、Elliott Alison M.、Bagaya Bernard S.

MRC/UVRI and LSHTM Uganda Research Unit||Department of Medical Microbiology, School of Biomedical Sciences, Makerere University College of Health SciencesMRC/UVRI and LSHTM Uganda Research Unit||Department of Internal Medicine, School of Medicine, Makerere University College of Health SciencesMRC/UVRI and LSHTM Uganda Research UnitMRC/UVRI and LSHTM Uganda Research Unit||Department of Medical Microbiology, School of Biomedical Sciences, Makerere University College of Health SciencesDepartment of Infection Biology, London School of Hygiene & Tropical MedicineMRC/UVRI and LSHTM Uganda Research Unit||Department of Clinical Research, London School of Hygiene & Tropical MedicineDepartment of Infection Biology, London School of Hygiene & Tropical MedicineMRC/UVRI and LSHTM Uganda Research UnitMRC/UVRI and LSHTM Uganda Research Unit||Department of Medical Microbiology, School of Biomedical Sciences, Makerere University College of Health Sciences||Department of Clinical Research, London School of Hygiene & Tropical MedicineMRC/UVRI and LSHTM Uganda Research Unit||Department of Clinical Research, London School of Hygiene & Tropical MedicineDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences

10.1101/680058

医药卫生理论医学研究方法微生物学

AntibodiesMycobacterium tuberculosisactive pulmonary tuberculosislatent tuberculosis infectionnon-specific responsesaviditypolyclonal activation

Kimuda Simon G.,Andia-Biraro Irene,Sebina Ismail,Egesa Moses,Smith Steven G.,Nalwoga Angela,Raynes John G.,Levin Jonathan,Cose Stephen,Elliott Alison M.,Bagaya Bernard S..Mycobacterium tuberculosis infection boosts B cell responses to unrelated pathogens[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/680058.点此复制

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