{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:55:26Z","timestamp":1791327326062,"version":"4.3.1"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Interferon (IFN)-inducible guanylate binding proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that the rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen<jats:named-content content-type=\"genus-species\">Chlamydia muridarum<\/jats:named-content>, so-called inclusions, remain free of GBPs and that<jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to<jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>inclusions nor restrict<jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>growth, we find that GBPs promote inflammasome activation in<jats:named-content content-type=\"genus-species\">C. muridarum-<\/jats:named-content>infected macrophages. We demonstrate that<jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>infections induce GBP-dependent pyroptosis through both caspase-11-dependent noncanonical and caspase-1-dependent canonical inflammasomes. Among canonical inflammasomes, we find that<jats:named-content content-type=\"genus-species\">C. muridarum<\/jats:named-content>and the human pathogen<jats:named-content content-type=\"genus-species\">Chlamydia trachomatis<\/jats:named-content>activate not only NLRP3 but also AIM2. Our data show that GBPs support fast-kinetics processing and secretion of interleukin-1\u03b2 (IL-1\u03b2) and IL-18 by the NLRP3 inflammasome but are dispensable for the secretion of the same cytokines at later times postinfection. Because IFN-\u03b3 fails to induce IL-1\u03b2 transcription, GBP-dependent fast-kinetics inflammasome activation can drive the preferential processing of constitutively expressed IL-18 in IFN-\u03b3-primed macrophages in the absence of prior Toll-like receptor stimulation. Together, our results reveal that GBPs control the kinetics of inflammasome activation and thereby shape macrophage responses to<jats:named-content content-type=\"genus-species\">Chlamydia<\/jats:named-content>infections.<\/jats:p>","DOI":"10.1128\/iai.00856-15","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T02:18:33Z","timestamp":1443493113000},"page":"4740-4749","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":149,"title":["Guanylate Binding Proteins Enable Rapid Activation of Canonical and Noncanonical Inflammasomes in Chlamydia-Infected Macrophages"],"prefix":"10.1128","volume":"83","author":[{"given":"Ryan","family":"Finethy","sequence":"first","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ine","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun K.","family":"Haldar","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel R.","family":"de Zoete","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA"},{"name":"Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Strowig","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA"},{"name":"Helmholtz Center for Infection Research, Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA"},{"name":"Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Yamadaoka, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma M.","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Coers","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro931"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2012.10.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2015.01.004"},{"key":"e_1_3_3_5_2","volume-title":"Global prevalence and incidence of selected curable sexually transmitted diseases: overview and estimates","author":"World Health Organization","year":"2011","unstructured":"World Health Organization. 2011. 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