Do MDL-1+ cells play a broad role in acute inflammation?
Peter A. Ward
Peter A. Ward
Published November 1, 2011; First published October 17, 2011
Citation Information: J Clin Invest. 2011;121(11):4234-4237. https://doi.org/10.1172/JCI60122.
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Do MDL-1+ cells play a broad role in acute inflammation?

Abstract

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.

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Peter A. Ward

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Figure 1

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.

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Proposed pathways that are MDL-1 dependent and lead to SIRS, liver injur...
In this scheme, release of both PMNs and MDL-1+ cells occurs in the bone marrow, under the influence of G-CSF (6). Upon entry into the bloodstream, MDL-1+ cells and PMNs traffic into the liver, which has been injured by injection of ConA. ConA initiates inflammation that damages the liver and sets the stage for accumulation of both PMNs and MDL-1+ cells. This damage is both PMN- and CD4+ T cell–dependent (17). As Cheung et al. describe (6), MDL-1+ cells produce NO and TNF-α, which injure the liver and also initiate SIRS and lead to multi-organ failure. This chain of events, which leads to the death of mice, can be greatly attenuated by use of neutralizing antibodies specific for MDL-1 or nitric oxide synthase, or antibodies specific for G-CSF. Also, NO scavengers greatly reduce lethality in this model (6).