Mouse granzyme K has pro-inflammatory potential

Cell Death Differ. 2011 Jul;18(7):1112-9. doi: 10.1038/cdd.2011.5. Epub 2011 Feb 11.


Granzymes (gzms) are key components of T-killer (Tc) cells believed to mediate pro-apoptotic activities. Recent evidence suggests that gzms also possess non-cytotoxic activities that contribute to host defense. In this study, we show that Tc cells from lymphocytic choriomeningitis virus (LCMV)-infected wild-type (wt) and gzm A/B-deficient mice express similar levels of gzmK protein, with both mouse strains efficiently controlling infection. GzmK, in recombinant form or secreted by ex vivo-derived LCMV-immune gzmAxB(-/-) Tc cells, lacks pro-apoptotic activity. Instead, gzmK induces primary mouse macrophages to process and secrete interleukin-1β, independent of the ATP receptor P2X(7). Together with the finding that IL-1Ra (Anakinra) treatment inhibits virus elimination but not generation of cytotoxic Tc cells in wt mice, the data suggest that Tc cells control LCMV through non-cytotoxic processes that involve gzmK.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenaviridae Infections / enzymology
  • Arenaviridae Infections / immunology*
  • Granzymes / deficiency
  • Granzymes / genetics
  • Granzymes / metabolism*
  • Inflammation Mediators / metabolism
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1beta / metabolism
  • Lymphocytic choriomeningitis virus* / drug effects
  • Lymphocytic choriomeningitis virus* / genetics
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Receptors, Purinergic P2X7 / deficiency
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes, Cytotoxic / enzymology
  • T-Lymphocytes, Cytotoxic / immunology*


  • Inflammation Mediators
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Purinergic P2X7
  • Recombinant Proteins
  • Granzymes