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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Boston Children's Hospital
  • Norwegian University of Science and Technology
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine

Keywords

  • Group A Streptococcus, Streptolysin O, Ubiquitin, IL-1β
Original languageEnglish
Pages (from-to)457-468
JournalJournal of Innate Immunity
Volume11
Issue number6
Early online date2019
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes

Related research output

Elsa Westerlund, 2019, Lund: Lund University: Faculty of Medicine. 84 p.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)

Related projects

View all (1)