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

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Streptolysin O induces the ubiquitination and degradation of pro-IL-1β. / Hancz, Dóra; Westerlund, Elsa; Valfridsson, Christine; Aemero, Getachew Melkamu; Bastiat-Sempe, Benedicte; Orning, Pontus; Lien, Egil; Wessels, Michael R.; Persson, Jenny J.

I: Journal of Innate Immunity, 2019.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Hancz, Dóra ; Westerlund, Elsa ; Valfridsson, Christine ; Aemero, Getachew Melkamu ; Bastiat-Sempe, Benedicte ; Orning, Pontus ; Lien, Egil ; Wessels, Michael R. ; Persson, Jenny J. / Streptolysin O induces the ubiquitination and degradation of pro-IL-1β. I: Journal of Innate Immunity. 2019.

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TY - JOUR

T1 - Streptolysin O induces the ubiquitination and degradation of pro-IL-1β

AU - Hancz, Dóra

AU - Westerlund, Elsa

AU - Valfridsson, Christine

AU - Aemero, Getachew Melkamu

AU - Bastiat-Sempe, Benedicte

AU - Orning, Pontus

AU - Lien, Egil

AU - Wessels, Michael R.

AU - Persson, Jenny J.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Group A Streptococcus

KW - Streptolysin O

KW - Ubiquitin, IL-1β

U2 - 10.1159/000496403

DO - 10.1159/000496403

M3 - Article

JO - Journal of Innate Immunity

T2 - Journal of Innate Immunity

JF - Journal of Innate Immunity

SN - 1662-811X

ER -