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Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

Nägeli, Andreas LU ; Bratanis, Eleni LU ; Karlsson, Christofer LU ; Shannon, Oonagh LU ; Kalluru, Raja LU ; Linder, Adam LU ; Malmström, Johan LU orcid and Collin, Mattias LU orcid (2019) In Journal of Experimental Medicine 216(7). p.1615-1629
Abstract

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased... (More)

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
216
issue
7
pages
1615 - 1629
publisher
Rockefeller University Press
external identifiers
  • pmid:31092533
  • pmid:31092533
  • scopus:85069265147
ISSN
1540-9538
DOI
10.1084/jem.20190293
language
English
LU publication?
yes
additional info
© 2019 Naegeli et al.
id
d014bbcf-4724-4f1d-9b03-cd6f5958f8e8
date added to LUP
2019-05-15 15:11:58
date last changed
2023-11-18 21:45:40
@article{d014bbcf-4724-4f1d-9b03-cd6f5958f8e8,
  abstract     = {{<p>Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.</p>}},
  author       = {{Nägeli, Andreas and Bratanis, Eleni and Karlsson, Christofer and Shannon, Oonagh and Kalluru, Raja and Linder, Adam and Malmström, Johan and Collin, Mattias}},
  issn         = {{1540-9538}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{1615--1629}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Experimental Medicine}},
  title        = {{Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis}},
  url          = {{https://lup.lub.lu.se/search/files/67943460/1615.full.pdf}},
  doi          = {{10.1084/jem.20190293}},
  volume       = {{216}},
  year         = {{2019}},
}