DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment

Host 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.

Source: ScienceNOW - October 18, 2018 Category: Science Authors: del Fresno, C., Saz-Leal, P., Enamorado, M., Wculek, S. K., Martinez-Cano, S., Blanco-Menendez, N., Schulz, O., Schulz, O., Gallizioli, M., Miro-Mur, F., Cano, E., Planas, A., Sancho, D. Tags: Immunology reports Source Type: news