Streptolysin O Induces the Ubiquitination and Degradation of Pro-IL-1β
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...
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Published in | Journal of innate immunity Vol. 11; no. 6; pp. 457 - 468 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
S. Karger AG
2019
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Subjects | |
Online Access | Get full text |
ISSN | 1662-811X 1662-8128 1662-8128 |
DOI | 10.1159/000496403 |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1662-811X 1662-8128 1662-8128 |
DOI: | 10.1159/000496403 |