{
  "abstract": "Citrobacter rodentium (CR) is a murine-specific enteric pathogen widely used to model infections of the attaching and effacing pathogens enteropathogenic and enterohaemorrhagic Escherichia coli. Infection induces colonic epithelial damage and inflammation that are resolved in resistant mice but result in severe disease and mortality in mice lacking interleukin-22 (IL-22). While IL-22-deficient (Il22−/−) mice succumb to CR infection due to dehydration, in part mediated by disruption of the barrier integrity by the type III secretion system (T3SS) effector EspF, the contribution of immunopathology to infection outcomes is not known. Here, using CR we tested whether dysregulated neutrophil responses drive disease progression in Il22−/− mice. We show that IL-22 deficiency is associated with progressive colonic pathology and increased neutrophil accumulation and activity in the colonic mucosa. Infection of mice with CR lacking the T3SS effector EspO, which is implicated in neutrophil recruitment, resulted in markedly reduced neutrophil accumulation and activity in Il22−/− mice without altering bacterial burden. Notably, CRΔespO infection led to reduced colonic inflammation and complete survival of Il22−/− mice. Consistent with these findings, CXCR2 antagonist treated Il22−/− mice displayed attenuated disease severity and delayed mortality. Together, we identified EspO as the second effector, alongside EspF, whose deletion results in survival of CR-infected Il22−/− mice. Moreover, these findings suggest that excessive neutrophil accumulation and activity are key drivers of lethality during CR infection in Il22−/− mice and that EspO amplifies neutrophil-dependent pathology within a vulnerable epithelial environment. Author summary: The immune system protects the intestine from infection, but excessive inflammation can itself cause severe tissue damage and disease. Interleukin-22 (IL-22) is a key cytokine that supports intestinal epithelial defence during infection with Citrobacter rodentium (CR), a bacterial pathogen commonly used to model human diarrhoeal disease. Mice lacking IL-22 develop severe lethal colitis following CR infection, but the role of immunopathology in this outcome has remained unclear. Here, we show that IL-22-deficient mice develop excessive accumulation and activation of neutrophils in the colon during CR infection. Rather than being protective, these exaggerated neutrophil responses drive lethal immunopathology. Using deletion of the bacterial virulence factor EspO as a pathogen-encoded means to attenuate neutrophil recruitment, we demonstrate that reducing colonic neutrophil accumulation is sufficient to prevent mortality. Our findings identify dysregulated neutrophil responses as key determinants of CR-induced lethality in IL-22-deficient mice and reveal how a bacterial effector can amplify harmful inflammation in a vulnerable host environment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Life Sciences, Imperial, London, United Kingdom",
    "Functional Proteomics Group, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom"
  ],
  "article_type": "Short Reports",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vishwas Mishra"
    },
    {
      "affs": [
        1
      ],
      "name": "Priyanka Biswas"
    },
    {
      "name": "Zuza Kozik"
    },
    {
      "name": "Jyoti Choudhary"
    },
    {
      "name": "Gad Frankel"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ds4aryejea64y.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014567",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014567",
  "id": "ds4aryejea64y",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014567",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1310|Escherichia coli research studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Digestive system/Gastrointestinal tract/Colon"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Histology"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteomics/Proteomic databases"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Neutrophils"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Neutrophils"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/Neutrophils"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Bacteriology/Bacterial lethality"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Bacteriology/Bacterial physiology/Secretion systems"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Microbial physiology/Bacterial physiology/Secretion systems"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Digestive system/Gastrointestinal tract/Colon"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Histology"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Neutrophils"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Virulence factors/Secretion systems"
    ],
    [
      "plos",
      "/Research and analysis methods/Database and informatics methods/Biological databases/Proteomic databases"
    ]
  ],
  "openalex": "W7206211661",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014567&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/ds4aryejea64y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "10.1371/journal.ppat.1014567",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014567"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    },
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "EspO-mediated neutrophil accumulation drives lethality during Citrobacter rodentium infection in interleukin-22-deficient mice",
  "title_text": "EspO-mediated neutrophil accumulation drives lethality during Citrobacter rodentium infection in interleukin-22-deficient mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/ds4aryejea64y",
  "venue": "PLOS Pathogens",
  "versions": []
}