Adrover, Jose Mdel Fresno, CarlosCrainiciuc, GeorgianaCuartero, Maria IsabelCasanova-Acebes, MariaWeiss, Linnea AHuerga-Encabo, HectorSilvestre-Roig, CarlosRossaint, JanCossio, ItziarLechuga-Vieco, Ana V.Garcia-Prieto, JaimeGomez-Parrizas, MonicaQuintana, Juan A.Ballesteros, IvanMartin-Salamanca, SandraAroca-Crevillen, AlejandraChong, Shu ZhenEvrard, MaximilienBalabanian, KarlLópez, JorgeBidzhekov, KirilBachelerie, FrançoiseAbad-Santos, FranciscoMuñoz-Calleja, CeciliaZarbock, AlexanderSoehnlein, OliverWeber, ChristianNg, Lai GuanLopez-Rodriguez, CristinaSancho, DavidMoro, Maria AngelesIbáñez, BorjaHidalgo, Andres2019-07-052019-07-052019-02Immunity. 2019; 50(2):390-4021074-7613http://hdl.handle.net/20.500.12105/7864Neutrophils 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.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Bmal1CXCR2CXCR4Candida albicansNeutrophilCircadian clockInfectionInflammationMyocardial infarctionNeutrophil agingAttribution-NonCommercial-NoDerivatives 4.0 Internacional30709741502402.e1010.1016/j.immuni.2019.01.0021097-4180Immunityopen access