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During bacterial infection, multiple mouse Gbps, human GBP2, and GBP5 support the activation of caspase\u20101\u2010containing inflammasome complexes or caspase\u20104 which trigger pyroptosis. Whether GBPs regulate other forms of cell death is not known. The apicomplexan parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    causes macrophage death through unidentified mechanisms. Here we report that\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    \u2010induced death of human macrophages requires GBP1 and its ability to target\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    parasitophorous vacuoles through its GTPase activity and prenylation. Mechanistically, GBP1 promoted\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    detection by AIM2, which induced GSDMD\u2010independent, ASC\u2010, and caspase\u20108\u2010dependent apoptosis. Identical molecular determinants targeted GBP1 to\n                    <jats:italic>Salmonella\u2010<\/jats:italic>\n                    containing vacuoles. GBP1 facilitated caspase\u20104 recruitment to\n                    <jats:italic>Salmonella<\/jats:italic>\n                    leading to its enhanced activation and pyroptosis. Notably, GBP1 could be bypassed by the delivery of\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    DNA or bacterial LPS into the cytosol, pointing to its role in liberating microbial molecules. GBP1 thus acts as a gatekeeper of cell death pathways, which respond specifically to infecting microbes. Our findings expand the immune roles of human GBPs in regulating not only pyroptosis, but also apoptosis.\n                  <\/jats:p>","DOI":"10.15252\/embj.2018100926","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T09:25:17Z","timestamp":1559294717000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":238,"title":["Human GBP1 is a microbe\u2010specific gatekeeper of macrophage apoptosis and pyroptosis"],"prefix":"10.1038","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-0367","authenticated-orcid":false,"given":"Daniel","family":"Fisch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Bando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Clough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Hornung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-9303","authenticated-orcid":false,"given":"Avinash R","family":"Shenoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-3442","authenticated-orcid":false,"given":"Eva\u2010Maria","family":"Frickel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,3]]},"reference":[{"key":"BFEMBJ2018100926_CR1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0952-7915(98)80114-3","volume":"10","author":"F Altare","year":"1998","unstructured":"Altare F, Jouanguy E, Lamhamedi S, Doffinger R, Fischer A, Casanova JL (1998) Mendelian susceptibility to mycobacterial infection in man. 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