{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:29:09Z","timestamp":1765888149675,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2019,5,6]]},"abstract":"<jats:p>Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent,<jats:italic>Neisseria meningitidis<\/jats:italic>, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1<jats:italic>\u03b2<\/jats:italic>(IL-1<jats:italic>\u03b2<\/jats:italic>), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome. Inflammasomes are activated by a number of microbial factors as well as danger molecules by a two-step mechanism\u2014priming and licensing of inflammasome activation\u2014but there are no data available regarding a role for inflammasome activation in meningococcal disease. The aim of this study was to investigate if<jats:italic>N. meningitidis<\/jats:italic>activates the inflammasome and, if so, the role of bacterial LOS in this activation. Cells were subjected to<jats:italic>N. meningitidis<\/jats:italic>, both wild-type (FAM20) and its LOS-deficient mutant (<jats:italic>lpxA<\/jats:italic>), and priming as well as licensing of inflammasome activation was investigated. The wild-type LOS-expressing parental FAM20 serogroup C<jats:italic>N. meningitidis<\/jats:italic>(FAM20) strain significantly enhanced the caspase-1 activity in human neutrophils and monocytes, whereas<jats:italic>lpxA<\/jats:italic>was unable to induce caspase-1 activity as well as to induce IL-1<jats:italic>\u03b2<\/jats:italic>release. While the<jats:italic>lpxA<\/jats:italic>mutant induced a priming response, measured as increased expression of<jats:italic>NLRP3<\/jats:italic>and<jats:italic>IL1B<\/jats:italic>, the LOS-expressing FAM20 further increased this priming. We conclude that although non-LOS components of<jats:italic>N. meningitidis<\/jats:italic>contribute to the priming of the inflammasome activity, LOS<jats:italic>per se<\/jats:italic>is to be considered as the central component of<jats:italic>N. meningitidis<\/jats:italic>virulence, responsible for both priming and licensing of inflammasome activation.<\/jats:p>","DOI":"10.1155\/2019\/6193186","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T18:56:08Z","timestamp":1557255368000},"page":"1-12","source":"Crossref","is-referenced-by-count":12,"title":["<i>Neisseria meningitidis<\/i>-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8060-2049","authenticated-orcid":true,"given":"Berhane Asfaw","family":"Idosa","sequence":"first","affiliation":[{"name":"iRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and 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