biostudies-literatureFisch DCancer Research UKFrancis Crick InstituteMedical Research CouncilThe Francis Crick InstituteJapan Agency for Medical Research and DevelopmentMinistry of Education, Culture, Sports, Science and TechnologyWellcome TrustBoehringer Ingelheim Fonds108008https://www.ebi.ac.uk/biostudies/studies/S-EPMC7435695biostudies-literatureUnknown32(6)Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively. The pathogen-proximal detection-mechanisms of GBP1 remain poorly understood, as humans lack functional immunity-related GTPases (IRGs) that assist murine Gbps. Here, we establish that GBP1 promotes the lysis of Tg-containing vacuoles and parasite plasma membranes, releasing Tg-DNA. In contrast, we show GBP1 targets cytosolic STm and recruits caspase-4 to the bacterial surface for its acCell reportsHuman GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death.PMC7435695MR/P028225/1MC_UP_1202/12FC001076FC001999217202/Z/19/ZJP18fk0108046MR/P022138/1108246/Z/15/Z100111007617K15677091664/B/10/ZJP18fk010804710004Shenoy AREncheva VYamamoto MFrickel EMSnijders APCollinson LMClough BBando HFisch DDomart MCfalseHuman GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death.Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively. The pathogen-proximal detection-mechanisms of GBP1 remain poorly understood, as humans lack functional immunity-related GTPases (IRGs) that assist murine Gbps. Here, we establish that GBP1 promotes the lysis of Tg-containing vacuoles and parasite plasma membranes, releasing Tg-DNA. In contrast, we show GBP1 targets cytosolic STm and recruits caspase-4 to the bacterial surface for its ac2020-01-01T00:00:00Z2020 Aug2026-05-02T21:02:48.8Z2020-08-24T07:07:27ZS-EPMC74356953278393610.1016/j.celrep.2020.108008