Adrover, Jose M.; del Fresno, Carlos; Crainiciuc, Georgiana; Isabel Cuartero, Maria; Casanova-Acebes, Maria; Weiss, Linnea A.; Huerga-Encabo, Hector; Silvestre-Roig, Carlos; Rossaint, Jan; Cossio, Itziar; Lechuga-Vieco, Ana V.; Garcia-Prieto, Jaime; Gomez-Parrizas, Monica; Quintana, Juan A.; Ballesteros, Ivan; Martin-Salamanca, Sandra; Aroca-Crevillen, Alejandra; Chong, Shu Zhen; Evrard, Maximilien; Balabanian, Karl; Lopez, Jörge; Bidzhekov, Kiril; Bachelerie, Frangoise; Abad-Santos, Francisco; Munoz-Calleja, Cecilia; Zarbock, Alexander; Soehnlein, Oliver; Weber, Christian; Ng, Lai Guan; Lopez-Rodriguez, Cristina; Sancho, David; Moro, Maria A.; Ibanez, Borja; Hidalgo, Andres (2019): A Neutrophil Timer Coordinates Immune Defense and Vascular Protection. In: Immunity, Vol. 50, No. 2 |
Abstract
Neutrophils eliminate pathogens efficiently but can inflict severe damage to the host if they over-activate within blood vessels. It is unclear how immunity solves the dilemma of mounting an efficient anti-microbial defense while preserving vascular health. Here, we identify a neutrophil-intrinsic program that enabled both. The gene Bmal1 regulated expression of the chemokine CXCL2 to induce chemokine receptor CXCR2-dependent diurnal changes in the transcriptional and migratory properties of circulating neutrophils. These diurnal alterations, referred to as neutrophil aging, were antagonized by CXCR4 (C-X-C chemokine receptor type 4) and regulated the outer topology of neutrophils to favor homeostatic egress from blood vessels at night, resulting in boosted anti-microbial activity in tissues. Mice engineered for constitutive neutrophil aging became resistant to infection, but the persistence of intravascular aged neutrophils predisposed them to thrombo-inflammation and death. Thus, diurnal compartmentalization of neutrophils, driven by an internal timer, coordinates immune defense and vascular protection.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 1074-7613 |
Language: | English |
ID Code: | 80474 |
Deposited On: | 15. Dec 2021 14:53 |
Last Modified: | 15. Dec 2021 14:53 |
- BASE
- Adrover, Jose M.
- del Fresno, Carlos
- Crainiciuc, Georgiana
- Isabel Cuartero, Maria
- Casanova-Acebes, Maria
- Weiss, Linnea A.
- Huerga-Encabo, Hector
- Silvestre-Roig, Carlos
- Rossaint, Jan
- Cossio, Itziar
- Lechuga-Vieco, Ana V.
- Garcia-Prieto, Jaime
- Gomez-Parrizas, Monica
- Quintana, Juan A.
- Ballesteros, Ivan
- Martin-Salamanca, Sandra
- Aroca-Crevillen, Alejandra
- Chong, Shu Zhen
- Evrard, Maximilien
- Balabanian, Karl
- Lopez, Jörge
- Bidzhekov, Kiril
- Bachelerie, Frangoise
- Abad-Santos, Francisco
- Munoz-Calleja, Cecilia
- Zarbock, Alexander
- Soehnlein, Oliver
- Weber, Christian
- Ng, Lai Guan
- Lopez-Rodriguez, Cristina
- Sancho, David
- Moro, Maria A.
- Ibanez, Borja
- Hidalgo, Andres
- Google Scholar
- Adrover, Jose M.
- del Fresno, Carlos
- Crainiciuc, Georgiana
- Isabel Cuartero, Maria
- Casanova-Acebes, Maria
- Weiss, Linnea A.
- Huerga-Encabo, Hector
- Silvestre-Roig, Carlos
- Rossaint, Jan
- Cossio, Itziar
- Lechuga-Vieco, Ana V.
- Garcia-Prieto, Jaime
- Gomez-Parrizas, Monica
- Quintana, Juan A.
- Ballesteros, Ivan
- Martin-Salamanca, Sandra
- Aroca-Crevillen, Alejandra
- Chong, Shu Zhen
- Evrard, Maximilien
- Balabanian, Karl
- Lopez, Jörge
- Bidzhekov, Kiril
- Bachelerie, Frangoise
- Abad-Santos, Francisco
- Munoz-Calleja, Cecilia
- Zarbock, Alexander
- Soehnlein, Oliver
- Weber, Christian
- Ng, Lai Guan
- Lopez-Rodriguez, Cristina
- Sancho, David
- Moro, Maria A.
- Ibanez, Borja
- Hidalgo, Andres