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

Science. 2018 Oct 19;362(6412):351-356. doi: 10.1126/science.aan8423.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / immunology*
  • Candidiasis / pathology*
  • Dendritic Cells / immunology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / physiology*
  • Mice
  • Mice, Mutant Strains
  • Necrosis
  • Neutrophil Infiltration / genetics
  • Neutrophil Infiltration / immunology*
  • Pancreas / immunology
  • Pancreas / microbiology
  • Pancreas / pathology*
  • Pancreatitis, Acute Necrotizing / microbiology
  • Pancreatitis, Acute Necrotizing / pathology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*


  • Clec9a protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic