Dataset Information

Inflammasome-independent IL-1β activation via staphopain A protease of Staphylococcus aureus

ABSTRACT: Interleukin-1β (IL-1β) is a pivotal mediator of innate immunity, essential for orchestrating the acute inflammatory response. While the canonical activation of IL-1β involves cleavage of its inactive precursor (pro-IL-1β) by the inflammatory cysteine protease caspase-1, certain bacterial proteases, such as those secreted by group A Streptococcus and Pseudomonas aeruginosa, can also activate pro-IL-1β. In this study, we demonstrate that infection of human N/TERT-1 immortalized keratinocytes by Staphylococcus aureus induces IL-1β processing independently of the classical inflammasome pathways. Biochemical analysis reveals that a secreted factor from S. aureus cleaves pro-IL-1β at a site proximal to the canonical caspase-1 cleavage site, rendering the cytokine bioactive. Specifically, we identify the secreted cysteine protease staphopain A as responsible for this cleavage. Our findings highlight a novel mechanism of inflammasome-independent IL-1β activation through microbial proteases, expanding the understanding of pathogen-host interactions in immune responses, specifically in the skin.

INSTRUMENT(S):

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Mario Oroshi

LAB HEAD: Veit Hornung

PROVIDER: PXD057289 | Pride | 2025-10-27

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MT32838_Horn_pro-IL-1b.pdf	Pdf
	MT32838_Horn_pro-IL-1b_3_01_13959.d.rar	Other
	MT32841_Horn_pro-IL-1b.pdf	Pdf
	MT32841_Horn_pro-IL-1b_4_01_13980.d.rar	Other
	MT32841_fragment_search.pdf	Pdf

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Publications

Inflammasome-independent IL-1β activation via staphopain A protease of Staphylococcus aureus.

Bauernfried Stefan S Komar Tobias T Sterle Katja K Tanzer Maria C MC Horswill Alexander R AR Mann Matthias M Hornung Veit V

The Journal of biological chemistry 20250808 10

Interleukin-1β (IL-1β) is a pivotal mediator of innate immunity, essential for orchestrating the acute inflammatory response. While the canonical activation of IL-1β involves cleavage of its inactive precursor (pro-IL-1β) by the inflammatory cysteine protease caspase-1, certain bacterial proteases, such as those secreted by group A Streptococcus and Pseudomonas aeruginosa, can also activate pro-IL-1β. In this study, we demonstrate that infection of human N/TERT-1 immortalized keratinocytes by St ...[more]

PMID: 40784452

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