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Streptolysin O induces the ubiquitination and degradation of pro-IL-1β

Hancz, Dóra LU ; Westerlund, Elsa LU ; Valfridsson, Christine LU ; Aemero, Getachew Melkamu LU ; Bastiat-Sempe, Benedicte ; Orning, Pontus ; Lien, Egil ; Wessels, Michael R. and Persson, Jenny J. LU (2019) In Journal of Innate Immunity 11(6). p.457-468
Abstract

Group A Streptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1β from infected macrophages. IL-1β is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage. Here, we use a macrophage infection model to show that SLO specifically induces ubiquitination and degradation of pro-IL-1β. Ubiquitination was dependent on SLO being released from the infecting bacterium, and pore formation by SLO was required but not sufficient... (More)

Group A Streptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1β from infected macrophages. IL-1β is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage. Here, we use a macrophage infection model to show that SLO specifically induces ubiquitination and degradation of pro-IL-1β. Ubiquitination was dependent on SLO being released from the infecting bacterium, and pore formation by SLO was required but not sufficient for the induction of ubiquitination. Our data provide evidence for a novel SLO-mediated mechanism of immune regulation, emphasizing the importance of this pore-forming toxin in bacterial virulence and pathogenesis.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Group A Streptococcus, Streptolysin O, Ubiquitin, IL-1β
in
Journal of Innate Immunity
volume
11
issue
6
pages
457 - 468
publisher
Karger
external identifiers
  • pmid:30889575
  • scopus:85063383637
ISSN
1662-811X
DOI
10.1159/000496403
project
On the effects of Streptococcal NAD+-glycohydrolase and Streptolysin O on macrophages
language
English
LU publication?
yes
id
e5ced56c-0af0-4b51-9822-e13eed545d06
date added to LUP
2019-04-11 10:16:04
date last changed
2024-04-16 03:50:46
@article{e5ced56c-0af0-4b51-9822-e13eed545d06,
  abstract     = {{<p>Group A Streptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1β from infected macrophages. IL-1β is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage. Here, we use a macrophage infection model to show that SLO specifically induces ubiquitination and degradation of pro-IL-1β. Ubiquitination was dependent on SLO being released from the infecting bacterium, and pore formation by SLO was required but not sufficient for the induction of ubiquitination. Our data provide evidence for a novel SLO-mediated mechanism of immune regulation, emphasizing the importance of this pore-forming toxin in bacterial virulence and pathogenesis.</p>}},
  author       = {{Hancz, Dóra and Westerlund, Elsa and Valfridsson, Christine and Aemero, Getachew Melkamu and Bastiat-Sempe, Benedicte and Orning, Pontus and Lien, Egil and Wessels, Michael R. and Persson, Jenny J.}},
  issn         = {{1662-811X}},
  keywords     = {{Group A Streptococcus; Streptolysin O; Ubiquitin, IL-1β}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{457--468}},
  publisher    = {{Karger}},
  series       = {{Journal of Innate Immunity}},
  title        = {{Streptolysin O induces the ubiquitination and degradation of pro-IL-1β}},
  url          = {{http://dx.doi.org/10.1159/000496403}},
  doi          = {{10.1159/000496403}},
  volume       = {{11}},
  year         = {{2019}},
}