Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

Astrid Hendriks; Priscilla F. Kerkman; Meri R.J. Varkila; Jelle L.G. Haitsma Mulier; Sara Ali; Thijs ten Doesschate; Thomas W. van der Vaart; Carla J.C. de Haas; Piet C. Aerts; Olaf L. Cremer; Marc J.M. Bonten; Victor Nizet; George Y. Liu; Jeroen D.C. Codée; Suzan H.M. Rooijakkers; Jos A.G. van Strijp; Nina M. van Sorge

Cell Reports Medicine (Sep 2024)

Glycan-specific IgM is critical for human immunity to Staphylococcus aureus

Astrid Hendriks,
Priscilla F. Kerkman,
Meri R.J. Varkila,
Jelle L.G. Haitsma Mulier,
Sara Ali,
Thijs ten Doesschate,
Thomas W. van der Vaart,
Carla J.C. de Haas,
Piet C. Aerts,
Olaf L. Cremer,
Marc J.M. Bonten,
Victor Nizet,
George Y. Liu,
Jeroen D.C. Codée,
Suzan H.M. Rooijakkers,
Jos A.G. van Strijp,
Nina M. van Sorge

Affiliations

Astrid Hendriks: Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands
Priscilla F. Kerkman: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Meri R.J. Varkila: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Jelle L.G. Haitsma Mulier: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Sara Ali: Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
Thijs ten Doesschate: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Thomas W. van der Vaart: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Carla J.C. de Haas: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Piet C. Aerts: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Olaf L. Cremer: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Marc J.M. Bonten: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Victor Nizet: Department of Pediatrics, University of California San Diego, San Diego, CA, USA
George Y. Liu: Department of Pediatrics, University of California San Diego, San Diego, CA, USA
Jeroen D.C. Codée: Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
Suzan H.M. Rooijakkers: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Jos A.G. van Strijp: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Nina M. van Sorge: Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands; Netherlands Reference Center for Bacterial Meningitis, Amsterdam UMC, location AMC, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, The Netherlands; Corresponding author

Journal volume & issue: Vol. 5, no. 9
p. 101734

Abstract

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Summary: Staphylococcus aureus is a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S. aureus surface glycan wall teichoic acid (WTA) and detect the presence of WTA-specific IgM and IgG antibodies in the plasma of healthy individuals. Functionally, WTA-specific IgM outperforms IgG in opsonophagocytic killing of S. aureus and protects against disseminated S. aureus bacteremia through passive immunization. In a clinical setting, patients with S. aureus bacteremia have significantly lower WTA-specific IgM but similar IgG levels compared to healthy controls. Importantly, low WTA-IgM levels correlate with disease mortality and impaired bacterial opsonization. Our findings may guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S. aureus infection.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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