{
  "abstract": "Caspase-1 and -11 are inflammatory caspases that trigger pyroptosis, yet in most infection models they confer only a modest survival benefit. We have proposed that caspase-1 and -11 evolved primarily to defend against ubiquitous environmental microbes that have not been under selective pressure to evade them, whereas host-adapted pathogens have evolved evasion strategies. Testing this idea is complicated because the inbred mouse strains used in most infection studies carry mutations in innate immune genes: i.e., C57BL/6 (B6) mice carry a loss-of-function Nramp1 allele, and 129 mice lack functional caspase-11. Here we generated B6 x 129 F1 hybrid mice, which are gene-sufficient at both Nramp1 and Casp11, and used them to measure the fold change in lethal dose ({triangleup}LD100) caused by caspase-1 and -11 deficiency for four pathogens on the B6, 129, and F1 backgrounds. Caspase-1 and -11 conferred little or no survival benefit against the host-adapted pathogens Listeria monocytogenes and Salmonella Typhimurium on any of the three backgrounds, apart from a modest benefit at the lowest S. Typhimurium inoculum in F1 mice. In contrast, caspase-1 and -11 were required to survive infection with the environmental pathogens Burkholderia thailandensis and Chromobacterium violaceum, where caspase-1 and -11 deficiency lowered the lethal dose by up to six orders of magnitude. The failure of caspase-1 and -11 against host-adapted pathogens therefore persists on a genetically robust hybrid background, supporting the view that a major evolutionary role of caspase-1 and -11 is defense against environmental microbes that have not been selected to evade them.",
  "abstract_shown": true,
  "affiliations": [
    "Duke University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "L. Li"
    },
    {
      "name": "B. D. McGlaughon"
    },
    {
      "name": "H. N. Larson"
    },
    {
      "name": "B. H. Koller"
    },
    {
      "affs": [
        0
      ],
      "name": "E. A. Miao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f1x82n2q5vvn9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.30.763184",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763184v1.full",
  "id": "f1x82n2q5vvn9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763184v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763184v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f1x82n2q5vvn9.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T00:20:41Z",
      "native_id": "10.64898/2026.10.30.763184",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763184v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Caspase-1 and -11 defend against environmental but not host-adapted pathogens in genetically complex mice",
  "title_text": "Caspase-1 and -11 defend against environmental but not host-adapted pathogens in genetically complex mice",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:11Z",
  "url": "https://research.draconitic.com/paper/f1x82n2q5vvn9",
  "venue": "bioRxiv",
  "versions": []
}