{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:56:28Z","timestamp":1791399388893,"version":"4.3.3"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neisseria gonorrhoeae is a common sexually transmitted pathogen that significantly impacts female fertility, neonatal health, and transmission of HIV worldwide. N. gonorrhoeae usually causes localized inflammation of the urethra and cervix by inducing production of IL-1\u03b2 and other inflammatory cytokines. Several NLR (nucleotide-binding domain, leucine-rich repeat) proteins are implicated in the formation of pro-IL-1\u03b2-processing complexes called inflammasomes in response to pathogens. We demonstrate that NLRP3 (cryopyrin, NALP3) is the primary NLR required for IL-1\u03b2\/IL-18 secretion in response to N. gonorrhoeae in monocytes. We also show that N. gonorrhoeae infection promotes NLRP3-dependent monocytic cell death via pyronecrosis, a recently described pathway with morphological features of necrosis, including release of the strong inflammatory mediator HMBG1. Additionally, N. gonorrhoeae activates the cysteine protease cathepsin B as measured by the breakdown of a cathepsin B substrate. Inhibition of cathepsin B shows that this protease is an apical controlling step in the downstream activities of NLRP3 including IL-1\u03b2 production, pyronecrosis, and HMGB1 release. Nonpathogenic Neisseria strains (Neisseria cinerea and Neisseria flavescens) do not activate NLRP3 as robustly as N. gonorrhoeae. Conditioned medium from N. gonorrhoeae contains factors capable of initiating the NLRP3-mediated signaling events. Isolated N. gonorrhoeae lipooligosaccharide, a known virulence factor from this bacterium that is elaborated from the bacterium in the form of outer membrane blebs, activates both NLRP3-induced IL-1\u03b2 secretion and pyronecrosis. Our findings indicate that activation of NLRP3-mediated inflammatory response pathways is an important venue associated with host response and pathogenesis of N. gonorrhoeae.<\/jats:p>","DOI":"10.4049\/jimmunol.0802696","type":"journal-article","created":{"date-parts":[[2009,5,4]],"date-time":"2009-05-04T16:48:20Z","timestamp":1241455700000},"page":"6460-6469","source":"Crossref","is-referenced-by-count":232,"title":["<i>Neisseria gonorrhoeae<\/i>\n                    Activates the Proteinase Cathepsin B to Mediate the Signaling Activities of the NLRP3 and ASC-Containing Inflammasome"],"prefix":"10.1093","volume":"182","author":[{"given":"Joseph A","family":"Duncan","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max Tze-Han","family":"Huang","sequence":"additional","affiliation":[{"name":"Curriculum in Oral Biology"},{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B","family":"Willingham","sequence":"additional","affiliation":[{"name":"Curriculum in Genetics and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T","family":"Bergstralh","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary A","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California at San Francisco, CA 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Frederick","family":"Sparling","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"},{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny P-Y","family":"Ting","sequence":"additional","affiliation":[{"name":"Curriculum in Oral Biology"},{"name":"Department of Microbiology and Immunology"},{"name":"Lineberger Comprehensive Cancer Center"},{"name":"Curriculum in Genetics and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,5,15]]},"reference":[{"key":"2026012806315450200_R1","first-page":"S263","article-title":"Antibiotic resistance in Neisseria gonorrhoeae.","volume-title":"Clin. 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