title: Mouse granzyme K has pro-inflammatory potential.
abstract: 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.
authors.affiliation: Metschnikoff Laboratory, Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
authors.forename: L T
authors.initials: LT
authors.lastname: Joeckel
authors.forename: R
authors.initials: R
authors.lastname: Wallich
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: D
authors.initials: D
authors.lastname: Sanchez-Martinez
authors.forename: F C
authors.initials: FC
authors.lastname: Weber
authors.forename: S F
authors.initials: SF
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Borner
authors.forename: J
authors.initials: J
authors.lastname: Pardo
authors.forename: C
authors.initials: C
authors.lastname: Froelich
authors.forename: M M
authors.initials: MM
authors.lastname: Simon
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000201:enzymology / Q000276:immunology*; D053804:Granzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins; D053804:Granzymes