期刊
NATURE IMMUNOLOGY
卷 21, 期 2, 页码 135-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-019-0571-2
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资金
- Intramural grants from the Severo Ochoa program (IGP-SO)
- Fundacio La Marato de TV3 [120/C/2015-20153032]
- Ministerio de Ciencia, Investigacion y Universidades (MCIU) [SAF2015-65607-R]
- Fondo Europeo de Desarrollo Regional
- MCIU [RTI2018-095497-B-I00, BES-2013-065550, SAF2015-68632-R]
- Fundacion La Caixa [HR17_00527]
- La Caixa Foundation [100010434, LCF/BQ/DR19/11740022]
- Instituto de Salud Carlos III [FIS PI17/01601]
- Wellcome Trust [206103/Z/17/Z]
- Deutsche Forschungsgemeinschaft [SFB1123-A1/A10]
- ERC-AdG [692511]
- Programa Red Guipuzcoana de Ciencia, Tecnologia e Informacion [SAF2017-84494-C2-R, 2018-CIEN-000058-01]
- Spanish State Research Agency [MDM-2017-0720]
- MCIU
- Pro-CNIC Foundation
- Severo Ochoa Center of Excellence (MEIC) [SEV-2015-0505]
- Wellcome Trust [206103/Z/17/Z] Funding Source: Wellcome Trust
- European Research Council (ERC) [692511] Funding Source: European Research Council (ERC)
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.
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