ArticleEMBO reports2025
Streptococcus pyogenes EVs induce the alternative inflammasome via caspase-4/-5 in human monocytes.
Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Extracellular Lipopolysaccharide Triggers the Release of Unconjugated Interferon-Stimulated Gene 15 (ISG15) Protein from Macrophages via Type-I Interferon/Caspase-4/Gasdermin-D Pathway.Pathogens (Basel, Switzerland) · 2026Article
- From biogenesis to host modulation: the expanding biology of oral streptococcal membrane vesicles.FEMS microbiology reviews · 2026Review
- The regulatory mechanism of NLRP3 inflammasome in the "immune paralytic-overactivation" imbalance in sepsis: the latest progress from molecular signaling to clinical translation.Frontiers in immunology · 2026Review
- Targeting SKAP2 restores sperm motility and morphology through modulating mitochondrial organization and cytoskeletal remodeling.Signal transduction and targeted therapy · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sensing of Gram-negative Extracellular Vesicles (EVs) by the innate immune system has been extensively studied in the past decade. In contrast, recognition of Gram-positive EVs by innate immune cells remains poorly understood. Comparative genome-wide transcriptional analysis in human monocytes uncovered that S. pyogenes EVs induce proinflammatory signatures that are markedly distinct from those of their parental cells. Among the 209 genes exclusively upregulated by EVs, caspase-5 prompted us to study inflammasome signaling pathways in depth. We show that lipoteichoic acid (LTA), a structural component of Gram-positive bacterial membranes present on EVs from S. pyogenes and other Gram-positive species, is sensed by TLR2 which triggers the alternative inflammasome composed of NLRP3 and the inflammatory caspases-4/-5 to mount an IL-1β response without inducing cell death. For S. pyogenes, we identify TLR8 as a sensor to mediate caspase-4/-5-dependent IL-1β secretion. Notably, inflammasome activation by intact bacteria is independent of the global virulence regulator CovS in monocytes. Overall, our study highlights a new role for TLR2 and caspase-4/-5 in the recognition of Gram-positive EVs in human monocytes.
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