Inflammasome-independent IL-1beta activation via staphopain A protease of Staphylococcus aureus
- Author(s)
- Bauernfried, S; Komar, T; Sterle, K; Tanzer, MC; Horswill, AR; Mann, M; Hornung, V;
- Details
- Publication Year 2025-08-08,Volume 301,Issue #10,Page 110574
- Journal Title
- Journal of Biological Chemistry
- Abstract
- Interleukin-1beta (IL-1beta) is a pivotal mediator of innate immunity, essential for orchestrating the acute inflammatory response. While the canonical activation of IL-1beta involves cleavage of its inactive precursor (pro-IL-1beta) 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-1beta. In this study, we demonstrate that infection of human N/TERT-1 immortalized keratinocytes by Staphylococcus aureus induces IL-1beta processing independently of the classical inflammasome pathways. Biochemical analysis reveals that a secreted factor from S. aureus cleaves pro-IL-1beta 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-1beta activation through microbial proteases, expanding the understanding of pathogen-host interactions in immune responses, specifically in the skin.
- Publisher
- Elsevier
- Keywords
- Nlrp1; Staphylococcus aureus; inflammasome; interleukin-1beta; keratinocytes; microbial proteases; staphopain A
- Research Division(s)
- Inflammation
- PubMed ID
- 40784452
- Publisher's Version
- https://doi.org/10.1016/j.jbc.2025.110574
- Open Access at Publisher's Site
https://doi.org/10.1016/j.jbc.2025.110574- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-08-19 01:46:00
Last Modified: 2025-10-20 01:59:37