Glycan-specific IgM is critical for human immunity to Staphylococcus aureus
Glycan-specific IgM is critical for human immunity to Staphylococcus aureus
Abstract Staphylococcus aureus is a major human pathogen but the immune factors that protect against it remain elusive. In particular, high opsonic IgG titers achieved in preclinical S. aureus animal immunization studies have consistently failed to translate to protection in human clinical trials. Here, we investigated the antibody responses to a conserved surface glycan, Wall Teichoic Acid (WTA). IgM and IgG antibodies specific to WTA were universally present in plasma from healthy individuals. Functionally, WTA-specific IgM outperformed IgG in opsonophagocytic killing of S. aureus and conferred passive protection against S. aureus infection in vivo. In the clinical setting, WTA-specific IgM responses, but not IgG responses, were significantly lower in S. aureus bacteremia patients compared to healthy individuals, correlated with mortality risk and showed impaired bacterial opsonization. Our findings can guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S. aureus infection.
Hendriks Astrid、Haitsma-Mulier Jelle L.G.、van der Vaart Thomas W.、de Haas Carla J.C.、van Strijp Jos A.G.、Ali Sara、ten Doesschate Thijs、Rooijakkers Suzan H.M.、Aerts Piet C.、Bonten Marc J.M.、Cod¨|e Jeroen D.C.、Cremer Olaf L.、Liu George Y.、van Sorge Nina M.、Kerkman Priscilla F.、Nizet Victor、Varkila Meri R.J.
Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location University of Amsterdam||Department of Medical Microbiology, University Medical Center Utrecht, Utrecht UniversityJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University||Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht UniversityJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University||Department of Internal Medicine, Division of Infectious Diseases, Amsterdam University Medical Center, University of AmsterdamDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht UniversityLeiden Institute of Chemistry, Leiden UniversityJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht UniversityDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht University||Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityLeiden Institute of Chemistry, Leiden UniversityDepartment of Intensive Care Medicine, University Medical Center Utrecht, Utrecht UniversityDepartment of Pediatrics, University of California San DiegoDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, location University of Amsterdam||Netherlands Reference Center for Bacterial Meningitis, Amsterdam UMC, location AMC||Amsterdam Institute for Infection and Immunity , Infectious DiseasesDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht UniversityDepartment of Pediatrics, University of California San DiegoJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University||Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University
基础医学微生物学
Hendriks Astrid,Haitsma-Mulier Jelle L.G.,van der Vaart Thomas W.,de Haas Carla J.C.,van Strijp Jos A.G.,Ali Sara,ten Doesschate Thijs,Rooijakkers Suzan H.M.,Aerts Piet C.,Bonten Marc J.M.,Cod¨|e Jeroen D.C.,Cremer Olaf L.,Liu George Y.,van Sorge Nina M.,Kerkman Priscilla F.,Nizet Victor,Varkila Meri R.J..Glycan-specific IgM is critical for human immunity to Staphylococcus aureus[EB/OL].(2025-03-28)[2025-05-25].https://www.biorxiv.org/content/10.1101/2023.07.14.548956.点此复制
评论