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

Autor:	Hendriks A; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands., Kerkman PF; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Varkila MRJ; 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., Haitsma Mulier JLG; 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., Ali S; Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands., Ten Doesschate T; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van der Vaart TW; 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., de Haas CJC; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Aerts PC; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Cremer OL; Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Bonten MJM; 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., Nizet V; Department of Pediatrics, University of California San Diego, San Diego, CA, USA., Liu GY; Department of Pediatrics, University of California San Diego, San Diego, CA, USA., Codée JDC; Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands., Rooijakkers SHM; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van Strijp JAG; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van Sorge NM; 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. Electronic address: n.m.vansorge@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Sep 17; Vol. 5 (9), pp. 101734.
DOI:	10.1016/j.xcrm.2024.101734
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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