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Peer-reviewedCC BY-NC-ND 4.0Nature Immunology

A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease

  • Hong Zheng1,2
  • Evan Maestri3
  • Andrew R. Moore4
  • Ananthakrishnan Ganesan1,2
  • Jeanna Enriquez3
  • Verónica Durán5
  • Shirit Einav5,6,7
  • Tom van der Poll8,9
  • Hjalmar R. Bouma10,11,12
  • Mihir R. Atreya13
  • Philip A. Efron14
  • Lyle L. Moldawer14
15 more authors
  • Jonathan Sevransky15
  • David W. Wright16
  • Ignacio Martin-Loeches17,18
  • Thomas Karvunidis19
  • Jeremiah Hinson20,21
  • David N. Hager22
  • Richard E. Rothman20
  • Evangelos J. Giamarellos-Bourboulis23,24
  • Timothy E. Sweeney25
  • Angela J. Rogers4
  • Saurabh Gombar26
  • Manoj V. Maddali27
  • Jonathan H. Chen2,28,29
  • Nigam Shah2,29,30
  • Purvesh Khatri1,2
30 affiliations
  1. 1Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA USA
  2. 2Division of Computational Medicine, Department of Medicine, School of Medicine, Stanford University, Stanford, CA USA
  3. 3Stanford Immunology Program, School of Medicine, Stanford University, Stanford, CA USA
  4. 4Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA USA
  5. 5Department of Microbiology and Immunology, Stanford University, Stanford, CA USA
  6. 6Chan Zuckerberg Biohub, San Francisco, CA USA
  7. 7Department of Medicine, Stanford University, Stanford, CA USA
  8. 8Center of Infection and Molecular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  9. 9Division of Infectious Diseases, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  10. 10Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  11. 11Department of Acute Care, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  12. 12Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  13. 13Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH USA
  14. 14Sepsis and Critical Illness Research Center and the SPIES Consortium, University of Florida College of Medicine, Gainesville, FL USA
  15. 15Division of Pulmonary, Allergy, Critical Care and Sleep and Emory Critical Care Center, Emory University, Atlanta, GA USA
  16. 16Department of Emergency Medicine, Emory University, Atlanta, GA USA
  17. 17Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James’s Hospital, Dublin, Ireland
  18. 18School of Medicine, Trinity College Dublin, Dublin, Ireland
  19. 191st Department of Internal Medicine, Faculty of Medicine, Teaching Hospital and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic
  20. 20Department of Emergency Medicine, The Johns Hopkins University, Baltimore, MD USA
  21. 21Danaher Diagnostics, Washington DC, USA
  22. 22Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD USA
  23. 234th Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece
  24. 24Hellenic Institute for the Study of Sepsis, Athens, Greece
  25. 25Inflammatix Inc, Sunnyvale, CA USA
  26. 26Atropos Health, New York, NY USA
  27. 27Division of Pulmonary and Critical Care Medicine, Piedmont Healthcare, Atlanta, GA USA
  28. 28Division of Hospital Medicine, Stanford University School of Medicine, Stanford, CA USA
  29. 29Clinical Excellence Research Center, Stanford School of Medicine, Stanford, CA USA
  30. 30Technology and Digital Solutions, Stanford Healthcare, Palo Alto, CA USA
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Abstract

Neutrophils, the most abundant leukocytes in human blood, have multifaceted roles in health and disease. Here we assembled a single-cell atlas of human neutrophils (SCAHN) by integrating transcriptome data from 1 million human neutrophils from 781 samples and 43 independent datasets. Using SCAHN, we identified multiple neutrophil subsets with distinct functions across tissues and robust changes in gene expression and subset proportions in infection, cancer, immune suppression and sex differences at single-cell resolution. Cross-species reference mapping of mouse and nonhuman primate neutrophils onto SCAHN revealed both conserved and species-specific features. Using 17,023 bulk blood transcriptome profiles from 40 datasets, we found that neutrophil-specific signatures predicted mortality in acutely ill patients at presentation, were associated with cancer diagnosis and survival, and correlated with metabolic dysfunction and long-term all-cause mortality. Our study highlights how neutrophil biology can improve immune risk stratification and develop effective diagnostic and therapeutic strategies.

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Cite

BibTeXRIS
BibTeX
@article{zheng2026singlecell,
  title = {{A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease}},
  author = {Hong Zheng and Evan Maestri and Andrew R. Moore and Ananthakrishnan Ganesan and Jeanna Enriquez and Verónica Durán and Shirit Einav and Tom van der Poll and Hjalmar R. Bouma and Mihir R. Atreya and Philip A. Efron and Lyle L. Moldawer and Jonathan Sevransky and David W. Wright and Ignacio Martin-Loeches and Thomas Karvunidis and Jeremiah Hinson and David N. Hager and Richard E. Rothman and Evangelos J. Giamarellos-Bourboulis and Timothy E. Sweeney and Angela J. Rogers and Saurabh Gombar and Manoj V. Maddali and Jonathan H. Chen and Nigam Shah and Purvesh Khatri},
  journal = {Nature Immunology},
  year = {2026},
  month = oct,
  doi = {10.1038/s41590-026-02671-8},
  url = {https://doi.org/10.1038/s41590-026-02671-8},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease
AU  - Hong Zheng
AU  - Evan Maestri
AU  - Andrew R. Moore
AU  - Ananthakrishnan Ganesan
AU  - Jeanna Enriquez
AU  - Verónica Durán
AU  - Shirit Einav
AU  - Tom van der Poll
AU  - Hjalmar R. Bouma
AU  - Mihir R. Atreya
AU  - Philip A. Efron
AU  - Lyle L. Moldawer
AU  - Jonathan Sevransky
AU  - David W. Wright
AU  - Ignacio Martin-Loeches
AU  - Thomas Karvunidis
AU  - Jeremiah Hinson
AU  - David N. Hager
AU  - Richard E. Rothman
AU  - Evangelos J. Giamarellos-Bourboulis
AU  - Timothy E. Sweeney
AU  - Angela J. Rogers
AU  - Saurabh Gombar
AU  - Manoj V. Maddali
AU  - Jonathan H. Chen
AU  - Nigam Shah
AU  - Purvesh Khatri
PY  - 2026
DA  - 2026/10/21
JO  - Nature Immunology
DO  - 10.1038/s41590-026-02671-8
UR  - https://doi.org/10.1038/s41590-026-02671-8
AB  - Neutrophils, the most abundant leukocytes in human blood, have multifaceted roles in health and disease. Here we assembled a single-cell atlas of human neutrophils (SCAHN) by integrating transcriptome data from 1 million human neutrophils from 781 samples and 43 independent datasets. Using SCAHN, we identified multiple neutrophil subsets with distinct functions across tissues and robust changes in gene expression and subset proportions in infection, cancer, immune suppression and sex differences at single-cell resolution. Cross-species reference mapping of mouse and nonhuman primate neutrophils onto SCAHN revealed both conserved and species-specific features. Using 17,023 bulk blood transcriptome profiles from 40 datasets, we found that neutrophil-specific signatures predicted mortality in acutely ill patients at presentation, were associated with cancer diagnosis and survival, and correlated with metabolic dysfunction and long-term all-cause mortality. Our study highlights how neutrophil biology can improve immune risk stratification and develop effective diagnostic and therapeutic strategies.
SN  - 1529-2908
SN  - 1529-2916
ER  -