ArticlePLoS pathogens2023
Constitutive secretion of pro-IL-18 allows keratinocytes to initiate inflammation during bacterial infection.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Dynamic tethering of M protein drives pathological inflammation during group A Streptococcus infections.PLoS pathogens · 2026Article
- Epithelial NLRP3 drives silica-induced lung injury and fibrosis through IL-18 and pro-fibrotic neutrophil recruitment.Particle and fibre toxicology · 2026Article
- The Ability of Probiotic Strain Escherichia coli O83:K24:H31 to Modulate Gut Homeostasis and Immune Function After Antibiotic-Induced Dysbiosis.Probiotics and antimicrobial proteins · 2026Article
- Staphylococcus aureus induces Gasdermin A-dependent keratinocyte pyroptosis.Nature communications · 2025Article
- Pentamidine inhibition of streptopain attenuatesMicrobiology spectrum · 2025Article
- IL-18 favors Th2 responses in sporotrichosis caused by Sporothrix globosa, prolonging the course of the disease.PLoS neglected tropical diseases · 2025Article
- Pentamidine inhibition of streptopain attenuatesbioRxiv : the preprint server for biology · 2025Article
- Proinflammatory synergy between protease and superantigen streptococcal pyogenic exotoxins.Infection and immunity · 2025Article
- Interplay between group AMicrobiology and molecular biology reviews : MMBR · 2024Review
- Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes.Journal of biomedical science · 2024Article
- Group A Streptococcus interactions with the host across time and space.Current opinion in microbiology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to pathogen invasion. Here, we characterized the proinflammatory cytokine repertoire produced by primary human keratinocytes and surrogate cell lines commonly used in vitro. Infection induces several cytokines and chemokines, but keratinocytes constitutively secrete IL-18 in a form that is inert (pro-IL-18) and lacks proinflammatory activity. Canonically, IL-18 activation and secretion are coupled through a single proteolytic event that is regulated intracellularly by the inflammasome protease caspase-1 in myeloid cells. The pool of extracellular pro-IL-18 generated by keratinocytes is poised to sense extracellular proteases. It is directly processed into a mature active form by SpeB, a secreted GAS protease that is a critical virulent factor during skin infection. This mechanism contributes to the proinflammatory response against GAS, resulting in T cell activation and the secretion of IFN-γ. Under these conditions, isolates of several other major bacterial pathogens and microbiota of the skin were found to not have significant IL-18-maturing ability. These results suggest keratinocyte-secreted IL-18 is a sentinel that sounds an early alarm that is highly sensitive to GAS, yet tolerant to non-invasive members of the microbiota.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.