Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation

Jose M. Adrover, Alejandra Aroca-Crevillen, Georgiana Crainiciuc, Fernando Ostos, Yeny Rojas-Vega, Andrea Rubio-Ponce, Catia Cilloniz, Elena Bonzon-Kulichenko, Enrique Calvo, Daniel Rico, Maria A. Moro, Christian Weber, Ignacio Lizasoain, Antoni Torres, Jesus Ruiz-Cabello, Jesus Vazquez, Andres Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

100 Citations (Web of Science)

Abstract

The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.

Hidalgo and colleagues describe a cell-intrinsic program that induces changes in the proteome, granule content and NET-forming capacity of neutrophils and is driven by the chemokine receptor CXCR2 and regulators of the circadian clock.

Original languageEnglish
Pages (from-to)135-144
Number of pages26
JournalNature Immunology
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • CIRCADIAN VARIATION
  • SECRETORY VESICLES
  • SERINE PROTEASES
  • GRANULE SUBSETS
  • MARROW
  • PATHOGENESIS
  • PLATELETS
  • ELASTASE
  • EFFECTOR
  • TRAPS

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