{
  "abstract": "Background\n\nSepsis is a highly heterogeneous syndrome characterized by variable immune dysregulation states, including hyperinflammation and immunosuppression. Previous immunotherapy attempts in sepsis have largely failed, likely due to a \"one-size-fits-all\" approach that ignores each patient's immune status. The recent ImmunoSep randomized clinical trial demonstrated that precision immunotherapy guided by the presence of either macrophage activation-like syndrome (MALS) or immune paralysis can improve early organ dysfunction in sepsis patients. However, the molecular mechanisms underlying these immune endotypes remain unclear.Objectives\n\nTo identify the immunological signatures that distinguish MALS and immune paralysis.Methods\n\nWe used single-cell RNA sequencing to profile circulating leukocytes of 6 healthy controls and 16 sepsis patients classified as MALS, immune paralysis or unclassified (when criteria for neither of these two immune endotypes were applicable). Classification was based on surrogate biomarkers ferritin and HLA-DR expression on monocytes. Thereafter, the transcriptional programs of these groups were compared.Results\n\nPronounced differences were detected mainly in the transcriptional signature of monocytes from these patients, with a clear distinction between MALS and immune paralysis. Unsupervised clustering analysis revealed the existence of MALS-specific monocyte clusters, as well as one sepsis-specific monocyte cluster that was linked to greater comorbidity burden and may reflect increased clinical vulnerability in sepsis. These findings were validated in two independent cohorts, in which urosepsis was characterized by heterogeneous MALS and immune paralysis monocyte signatures. Moreover, MALS-specific monocyte clusters showed overlapping transcriptional signatures with severe COVID-19.Conclusions\n\nOur findings shed light on the heterogeneous immune landscape underlying sepsis and provide opportunities for patient stratification for future therapeutic development.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein 8, Nijmegen, 6525GA, The Netherlands.",
    "Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.",
    "TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.",
    "Research Centre Innovations in Care, Rotterdam University of Applied Sciences, Rotterdam, The Netherlands.",
    "Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein 8, Nijmegen, 6525GA, The Netherlands. tristan.couwenbergh@radboudumc.nl.",
    "4th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece.",
    "Department of Intensive Care and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.",
    "Hellenic Institute for the Study of Sepsis, Athens, Greece.",
    "Department of Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Inge Grondman"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Valerie A C M Koeken"
    },
    {
      "affs": [
        4
      ],
      "name": "Tristan Couwenbergh"
    },
    {
      "affs": [
        5
      ],
      "name": "Athanasios Karageorgos"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Wenchao Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Nikolaos Antonakos"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Bowen Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Georgia Damoraki"
    },
    {
      "affs": [
        6
      ],
      "name": "Wouter A van der Heijden"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Cheng-Jian Xu"
    },
    {
      "affs": [
        5,
        7
      ],
      "name": "Evangelos J Giamarellos-Bourboulis"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yang Li"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Mihai G Netea"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/etqa4k4kk9nfw.bib",
  "cited_by": 0,
  "doi": "10.1186/s13054-026-06229-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13729535",
  "id": "etqa4k4kk9nfw",
  "issns": [
    "1364-8535",
    "1466-609X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42972580",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7172110726",
  "pdf_url": "https://europepmc.org/articles/PMC13729535?pdf=render",
  "pmcid": "PMC13729535",
  "pmid": "42972580",
  "published": "2026-08-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/etqa4k4kk9nfw.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:45Z",
      "native_id": "MED:42972580",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42972580"
    },
    {
      "first_seen": "2026-11-07T12:22:16Z",
      "native_id": "PMC13729535",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13054-026-06229-w"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Distinct transcriptomic signatures discriminate hyperinflammation from immune paralysis in sepsis: a single-cell RNA sequencing study.",
  "title_text": "Distinct transcriptomic signatures discriminate hyperinflammation from immune paralysis in sepsis: a single-cell RNA sequencing study.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:16Z",
  "url": "https://research.draconitic.com/paper/etqa4k4kk9nfw",
  "venue": "Critical care (London, England)",
  "versions": []
}