{
  "id": 14232699,
  "title": "Human caspase-4 and caspase-5 assemble into non-canonical inflammasomes in response to overlapping and distinct LPS structures",
  "url": "https://urgent.news/2026/10/13/human-caspase-4-and-caspase-5-assemble-into-non-canonical",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-13T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756901v1?rss=1"
  },
  "original_language": "en",
  "account": "In response to bacterial lipopolysaccharide (LPS) exposure, human caspase-4 (CASP4) and caspase-5 (CASP5) assemble into non-canonical inflammasomes called supramolecular organizing centers (SMOCs), according to recent research. Like mouse caspase-11 (Casp11), caspases-4 and -5 form SMOCs in a catalytically dependent manner when activated by LPS.\n\nWhile CASP11 oligomerizes in response to cytosolic LPS, CASP4 and CASP5 exhibit differential responses to distinct LPS structural variants. These variations fail to activate CASP11 but induce SMOC formation when activating LPS structures are present. Importantly, transgenic mice expressing CASP4 instead of Casp11 show more effective control of Francisella novicida, a rodent pathogen whose LPS evades detection by TLR4 and Casp11.\n\nHowever, mice expressing CASP4 are more susceptible to sepsis when exposed to E. coli that carries a lipid A variant which fails to activate TLR4 and Casp11. These findings suggest that human CASP4 and CASP5 have evolved to respond to a wider range of LPS structures compared to mouse Casp11. The study highlights a potential tradeoff between systemic inflammation and bacterial infection control, which may explain the observed differences between human and mouse innate immune responses.\n\nThe findings may help inform the development of targeted therapeutic strategies for gram-negative bacterial infections and sepsis, ultimately benefiting human health.",
  "summary": "Innate immune sensing of bacterial lipopolysaccharide (LPS) is critical to host defense, but a dysregulated response can lead to sepsis, a life-threatening condition associated with multiple organ failure and shock. LPS is sensed at the cell surface by Toll-Like Receptor 4 (TLR4) and in the cytosol by mouse caspase-11 (Casp11) or its human orthologs, caspase-4 and 5 (CASP4/5). In response to…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}