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. 2019 Feb 19;50(2):390-402.e10.
doi: 10.1016/j.immuni.2019.01.002. Epub 2019 Jan 29.

A Neutrophil Timer Coordinates Immune Defense and Vascular Protection

José M Adrover  1 , Carlos Del Fresno  2 , Georgiana Crainiciuc  1 , Maria Isabel Cuartero  3 , María Casanova-Acebes  4 , Linnea A Weiss  5 , Hector Huerga-Encabo  6 , Carlos Silvestre-Roig  7 , Jan Rossaint  8 , Itziar Cossío  1 , Ana V Lechuga-Vieco  2 , Jaime García-Prieto  2 , Mónica Gómez-Parrizas  2 , Juan A Quintana  1 , Ivan Ballesteros  1 , Sandra Martin-Salamanca  1 , Alejandra Aroca-Crevillen  1 , Shu Zhen Chong  9 , Maximilien Evrard  9 , Karl Balabanian  10 , Jorge López  11 , Kiril Bidzhekov  12 , Françoise Bachelerie  10 , Francisco Abad-Santos  13 , Cecilia Muñoz-Calleja  11 , Alexander Zarbock  8 , Oliver Soehnlein  7 , Christian Weber  14 , Lai Guan Ng  9 , Cristina Lopez-Rodriguez  6 , David Sancho  2 , María A Moro  3 , Borja Ibáñez  15 , Andrés Hidalgo  16
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Free article

A Neutrophil Timer Coordinates Immune Defense and Vascular Protection

José M Adrover et al. Immunity. .
Free article

Erratum in

  • A Neutrophil Timer Coordinates Immune Defense and Vascular Protection.
    Adrover JM, Del Fresno C, Crainiciuc G, Cuartero MI, Casanova-Acebes M, Weiss LA, Huerga-Encabo H, Silvestre-Roig C, Rossaint J, Cossío I, Lechuga-Vieco AV, García-Prieto J, Gómez-Parrizas M, Quintana JA, Ballesteros I, Martin-Salamanca S, Aroca-Crevillen A, Chong SZ, Evrard M, Balabanian K, López J, Bidzhekov K, Bachelerie F, Abad-Santos F, Muñoz-Calleja C, Zarbock A, Soehnlein O, Weber C, Ng LG, Lopez-Rodriguez C, Sancho D, Moro MA, Ibáñez B, Hidalgo A. Adrover JM, et al. Immunity. 2019 Nov 19;51(5):966-967. doi: 10.1016/j.immuni.2019.11.001. Immunity. 2019. PMID: 31747583 No abstract available.

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.

Keywords: Bmal1; CXCR2; CXCR4; Candida albicans; Neutrophil; circadian clock; infection; inflammation; myocardial infarction; neutrophil aging.

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