Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis

ABSTRACT: The guanylate-binding protein (GBP) family of interferon-inducible GTPases promotes antimicrobial immunity and cell death. During bacterial infection, multiple mouse Gbps, human GBP2 and GBP5 support the activation of caspase-1-containing inflammasome complexes or caspase-4 which trigger pyroptosis. Whether GBPs regulate other forms of cell death is not known. The apicomplexan parasite Toxoplasma gondii causes macrophage death through unidentified mechanisms. Here we report that Toxoplasma-induced death of human macrophages requires GBP1, and its ability to target Toxoplasma parasitophorous vacuoles through its GTPase activity and prenylation. Mechanistically, GBP1 promoted Toxoplasma detection by AIM2, which induced GSDMD-independent, ASC- and caspase-8-dependent apoptosis. Identical mole

SUBMITTER: Daniel Fisch 

PROVIDER: S-SCDT-EMBOJ-2018-100926 | biostudies-other |

REPOSITORIES: biostudies-other