Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress

Elisa Montaldo, Eleonora Lusito, Valentina Bianchessi, Nicoletta Caronni, Serena Scala, Luca Basso-Ricci, Carla Cantaffa, Alice Masserdotti, Mattia Barilaro, Simona Barresi, Marco Genua, Francesco Maria Vittoria, Giulia Barbiera, Dejan Lazarevic, Carlo Messina, Elisabetta Xue, Sarah Marktel, Cristina Tresoldi, Raffaella Milani, Paola RonchiSalvatore Gattillo, Luca Santoleri, Raffaella Di Micco, Andrea Ditadi, Giulio Belfiori, Francesca Aleotti, Matteo Maria Naldini, Bernhard Gentner, Elisa Gardiman, Nicola Tamassia, Marco Antonio Cassatella, Andrés Hidalgo, Immanuel Kwok, Lai Guan Ng, Stefano Crippa, Massimo Falconi, Francesca Pettinella, Patrizia Scapini, Luigi Naldini, Fabio Ciceri, Alessandro Aiuti, Renato Ostuni

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.

Original languageEnglish
Pages (from-to)1470-1483
Number of pages14
JournalNature Immunology
Volume23
Issue number10
DOIs
StatePublished - Oct 2022
Externally publishedYes

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