Mouse granzyme K has pro-inflammatory potential

Markus Simon (1) , Lars T Joeckel (1) , Reinhard Wallich (1) , Julián Pardo (1) , Praxedis Martin (1) , Christoph Borner (1) , Christopher Froelich (1) , Stefan F Martin (1) , Felix C Weber (1) , Diego Sánchez (1)

1 Metschnikoff laboratory

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. Here we show that Tc cells from lymphocytic choriomeningitis virus (LCMV)-infected wild type and granzyme 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 P2X7. Together with the finding that IL-1Ra (Anakinra) treatment inhibits virus elimination but not generation of cytotoxic Tc cells in wild type mice, the data suggest that Tc cells control LCMV via non-cytotoxic processes that involves gzmK.

Mots clés: T killer cell; virus control; orphan granzymes; cell death; inflammation

Markus Simon, Lars T Joeckel, Reinhard Wallich, Julián Pardo, Praxedis Martin, et al.. Mouse granzyme K has pro-inflammatory potential. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2011.5⟩. ⟨hal-00614316⟩