{
  "abstract": "Pneumonia is the leading infectious disease killer worldwide and commonly requires admission to critical care. Despite its prevalence, the underpinning biology of severe pneumonia remains incompletely understood. Here we perform multifaceted assessments of bronchoalveolar transcriptome, cytokines, microbiology, and clinical features to biologically characterise a cohort of patients with suspected severe pneumonia. Our data implicate three lung-restricted transcriptionally defined severe pneumonia endotypes (termed 'Pneumotypes' (Pn)). All three Pneumotypes have comparable clinical presentations and severity of respiratory failure but experience divergent outcomes. Pn1, the most common, is characterised by low alveolar cytokines, expanded tolerogenic macrophages and epithelial damage. Pn3 is characterised by immature neutrophil infiltration, IL-6-STAT3 activation and longer duration of mechanical ventilation. Pn2 displays the fastest resolution, exhibiting a balanced immune response and epithelial-endothelial repair signatures. We identify and validate mechanistically distinct phenotypes in the lungs of patients with suspected pneumonia and acute lung injury, implicating targets for personalised therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Perioperative, Acute, Critical Care and Emergency Medicine, Department of Medicine, University of Cambridge, Cambridge, UK",
    "University of Cambridge",
    "Cambridge Institute of Therapeutic Immunology & Infectious Disease, Department of Medicine, University of Cambridge, Cambridge, UK",
    "Queen Mary University of London",
    "European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK",
    "Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK",
    "The School of Medicine, University of St Andrews, St Andrews, UK",
    "Clinical Microbiology and Public Health Laboratory, UK Health Security Agency, Cambridge",
    "Clinical Microbiology and Public Health Laboratory, UK Health Security Agency, Cambridge, UK",
    "Addenbrookes Hospital, Cambridge",
    "John V Farman Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK",
    "Department of Respiratory Medicine, Addenbrooke's Hospital, Cambridge, UK",
    "Wellcome-Sanger Institute, Cambridge",
    "Department of Pneumology, University Hospitals Leuven, Leuven, Belgium",
    "Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium",
    "Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium",
    "VIB Center for Cancer Biology, VIB, Leuven, Belgium",
    "Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium",
    "Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium",
    "A*STAR Infectious Diseases Labs (A*STAR IDL), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore",
    "Centre for Translational Stem Cell Biology, LKS Faculty of Medicine, Hong Kong University, Hong Kong, China",
    "Division of Perioperative, Acute, Critical Care and Emergency Medicine, Department of Medicine, University of Cambridge, Cambridge, UK. ac926@cam.ac.uk",
    "John V Farman Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK. ac926@cam.ac.uk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mark Jeffrey"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Josefin Bartholdson Scott",
      "orcid": "0000-0003-3380-4446"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Shyamanova Mazumdar",
      "orcid": "0009-0009-9692-9562"
    },
    {
      "affs": [
        2,
        4,
        1
      ],
      "name": "Richard Joseph White",
      "orcid": "0000-0003-1842-412X"
    },
    {
      "affs": [
        2,
        5,
        1
      ],
      "name": "Ellen E. Higginson",
      "orcid": "0000-0001-9218-1627"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Mailis Maes",
      "orcid": "0000-0002-0266-6557"
    },
    {
      "affs": [
        2,
        6,
        1
      ],
      "name": "Sally Forrest",
      "orcid": "0000-0001-6918-5216"
    },
    {
      "affs": [
        2,
        5,
        7
      ],
      "name": "Joana Pereira-Dias"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Surendra Parmar",
      "orcid": "0000-0002-3248-7066"
    },
    {
      "affs": [
        8,
        7
      ],
      "name": "Emma Heasman-Hunt"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Martin D. Curran"
    },
    {
      "affs": [
        10,
        9
      ],
      "name": "Petra Polgarova",
      "orcid": "0000-0002-5808-7482"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Jurgen Herre"
    },
    {
      "affs": [
        13,
        14,
        1
      ],
      "name": "Els Wauters",
      "orcid": "0000-0002-0115-0030"
    },
    {
      "affs": [
        15,
        16,
        1
      ],
      "name": "Diether Lambrechts",
      "orcid": "0000-0002-3429-302X"
    },
    {
      "affs": [
        13,
        15,
        9
      ],
      "name": "Pierre Van Mol"
    },
    {
      "affs": [
        17,
        18,
        1
      ],
      "name": "Cato Jacobs"
    },
    {
      "affs": [
        17,
        18
      ],
      "name": "Joost Wauters",
      "orcid": "0000-0002-5983-3897"
    },
    {
      "affs": [
        5
      ],
      "name": "Emma E. Davenport",
      "orcid": "0000-0002-8768-346X"
    },
    {
      "affs": [
        19
      ],
      "name": "Stephen Baker"
    },
    {
      "affs": [
        2,
        20
      ],
      "name": "Gordon Dougan B",
      "orcid": "0000-0003-0022-965X"
    },
    {
      "affs": [
        10
      ],
      "name": "Vilas Navapurkar"
    },
    {
      "affs": [
        21,
        22
      ],
      "name": "Andrew Conway Morris",
      "orcid": "0000-0002-3211-3216"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8697eht41mfgx.bib",
  "cited_by": 9,
  "doi": "10.1038/s41467-026-74190-x",
  "fulltext_url": null,
  "id": "8697eht41mfgx",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-74190-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Pneumonia and Respiratory Infections"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-74190-x.pdf",
  "pmcid": "PMC13291267",
  "pmid": "42337236",
  "published": "2026-06-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/8697eht41mfgx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:56Z",
      "native_id": "W4402167172",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-74190-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Pneumonia and Respiratory Infections",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes",
  "title_text": "Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:15Z",
  "url": "https://research.draconitic.com/paper/8697eht41mfgx",
  "venue": "Nature Communications",
  "versions": []
}