F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells

Immunity. 2012 Apr 20;36(4):635-45. doi: 10.1016/j.immuni.2012.03.008. Epub 2012 Apr 5.


Sterile inflammation can be initiated by innate immune recognition of markers of tissue injury termed damage-associated molecular patterns (DAMPs). DAMP recognition by dendritic cells (DCs) has also been postulated to lead to T cell responses to foreign antigens in tumors or allografts. Many DAMPs represent intracellular contents that are released upon cell damage, notably after necrosis. In this regard, we have previously described DNGR-1 (CLEC9A) as a DC-restricted receptor specific for an unidentified DAMP that is exposed by necrotic cells and is necessary for efficient priming of cytotoxic T cells against dead cell-associated antigens. Here, we have shown that the DNGR-1 ligand is preserved from yeast to man and corresponds to the F-actin component of the cellular cytoskeleton. The identification of F-actin as a DNGR-1 ligand suggests that cytoskeletal exposure is a universal sign of cell damage that can be targeted by the innate immune system to initiate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / genetics
  • Actins / metabolism*
  • Dendritic Cells / metabolism
  • HeLa Cells
  • Humans
  • Immunity, Innate
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism*
  • Necrosis / immunology
  • Necrosis / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Mitogen / immunology*
  • Receptors, Mitogen / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • T-Lymphocytes, Cytotoxic / immunology


  • Actins
  • CLEC9a protein, human
  • Lectins, C-Type
  • RNA, Small Interfering
  • Receptors, Mitogen
  • Saccharomyces cerevisiae Proteins