Dengue virus (DV) reacts with myeloid DAP12-associating lectin–1 (MDL-1) on immature polymorphonuclear leukocytes. Interaction of DV with MDL-1+ cells triggers systemic inflammatory response syndrome (SIRS) and dengue shock syndrome (DSS), with subsequent multi-organ failure. In this issue of the JCI, Cheung et al. find that sterile acute liver injury in mice is associated with the accumulation of MDL-1+ cells and that triggering of these cells by DV or an MDL-1–specific agonist antibody leads to SIRS, shock, and death. These findings may have broad mechanistic and therapeutic implications for the development of SIRS, sepsis, and shock in humans exposed to a wide array of infectious and non-infectious conditions.
Peter A. Ward
Proposed pathways that are MDL-1 dependent and lead to SIRS, liver injury, and lethal shock in the setting of ConA-induced acute liver injury.