Detecting Danger

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Science  18 May 2012:
Vol. 336, Issue 6083, pp. 782
DOI: 10.1126/science.336.6083.782-c

Besides responding to infections, the immune system can also recognize tissue injury in the absence of any infectious agents. Examples of this include antitumor immunity and responses to transplanted organs. During these “sterile” responses, the immune system is triggered by so-called DAMPs, danger-associated molecular patterns. These include intracellular contents such as ATP and HMGB1 that are released upon cell damage or death. The C-type lectin DNGR-1 (Clec9a) is a receptor expressed by certain subsets of dendritic cells that is required for the presentation of antigens derived from necrotic cells to T cells. What it recognizes on dying cells, however, has remained a mystery. After a rather challenging hunt, Zhang et al. and Ahrens et al. now report that DNGR-1, recognized actin filaments. Monomeric actin, or G-actin, was not recognized by DNGR-1, and actin binding proteins such as spectrin enhanced DNGR-1 recognition of actin. The identification of F-actin as a ligand for DNGR-1 reinforces the idea that molecules that normally play a housekeeping role in healthy cells are able to activate the immune system when released into the extracellular milieu. Although this often triggers a controlled immune response that promotes tissue repair, alterations in this response could drive inflammation and contribute to disease processes.

Immunity 36, 635; 646 (2012).

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