| First Author | Del Fresno C | Year | 2018 |
| Journal | Science | Volume | 362 |
| Issue | 6412 | Pages | 351-356 |
| PubMed ID | 30337411 | Mgi Jnum | J:266909 |
| Mgi Id | MGI:6257197 | Doi | 10.1126/science.aan8423 |
| Citation | Del Fresno C, et al. (2018) DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment. Science 362(6412):351-356 |
| abstractText | 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. |
