del Fresno, CarlosSanz-Leal, PaulaEnamorado, MichelWculek, Stefanie KMartinez-Cano, SaraiBlanco-Menendez, NoeliaSchulz, OliverGallizioli, MattiaMiró-Mur, FrancescCano, EvaPlanas, AnnaSancho, David2018-10-222018-10-222018-10-19Science. 2018; 362(6412):351-3560036-8075http://hdl.handle.net/20.500.12105/6502Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses tissue damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell-independent and attributable to increased neutrophilia in DNGR-1-deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1-mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.engAMhttp://creativecommons.org/licenses/by-nc-sa/4.0/Atribución-NoComercial-CompartirIgual 4.0 Internacional303374113626412351-35610.1126/science.aan84231095-9203Scienceopen access