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

Carlos Del Fresno, Paula Saz-Leal, Michel Enamorado, Stefanie K. Wculek, Sarai Martínez-Cano, Noelia Blanco-Menéndez, Oliver Schulz, Mattia Gallizioli, Francesc Miró-Mur, Eva Cano, Anna Planas, David Sancho

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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 hostdamaging 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.

Original languageEnglish
Pages (from-to)351-356
Number of pages6
Issue number6412
StatePublished - 19 Oct 2018
Externally publishedYes


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