UMMS Affiliation

Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

2019-03-19

Document Type

Article

Disciplines

Bacteriology | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Immunopathology

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-1beta from infected macrophages. IL-1beta 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-1beta. 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.

Keywords

Group A Streptococcus, Streptolysin O, Ubiquitin, IL-1β

Rights and Permissions

© 2019 The Author(s) Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

DOI of Published Version

10.1159/000496403

Source

J Innate Immun. 2019 Mar 19:1-12. doi: 10.1159/000496403. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Journal of innate immunity

Related Resources

Link to Article in PubMed

PubMed ID

30889575

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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