Neutralization of Streptolysin S-Dependent and Independent Inflammatory Cytokine IL-1β Activity Reduces Pathology During Early Group A Streptococcal Skin Infection

Frontiers in Cellular and Infection Microbiology
Rebecca A FlahertyShaun W Lee

Abstract

The bacterial pathogen Group A Streptococcus (GAS) has been shown to induce a variety of human diseases ranging in severity from pharyngitis to toxic shock syndrome and necrotizing fasciitis. GAS produces a powerful peptide toxin known as Streptolysin S (SLS). Though long recognized as a potent cytolysin, recent evidence from our lab has shown that SLS-dependent cytotoxicity is mediated through activation of the pro-inflammatory mediators p38 MAPK and NFκB. These findings led us to hypothesize that activation of p38 MAPK and NFκB signaling drive the production of pro-inflammatory cytokines which, in turn, serve as positive feedback signals to initiate cytotoxicity in infected host cells. To address this hypothesis, we utilized a cytokine array to characterize the SLS-dependent pro-inflammatory cytokine response to GAS infection in human keratinocytes. From these studies, IL-1β was found to be markedly upregulated in the presence of SLS, and further investigation revealed that this cytokine contributes to cytotoxicity in human keratinocytes during infection. Subcutaneous infection studies were performed in mice to address the physiological impact of increased IL-1β production. These studies demonstrated that IL-1β is produced du...Continue Reading

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Citations

Dec 26, 2018·American Journal of Reproductive Immunology : AJRI·Jessica A SuttonDavid M Aronoff
Jun 23, 2021·Cellular Microbiology·Johanna RichterMark J Walker
Oct 1, 2021·Microbiology and Immunology·Atsushi Tabata, Hideaki Nagamune
Mar 20, 2019·Journal of Innate Immunity·Dóra HanczJenny J Persson

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Methods Mentioned

BETA
Antibody Array
ELISA

Software Mentioned

Graph Pad Prism

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