The NLRC4 inflammasome is a crucial part of the innate immune response against bacterial infections. We found that NLRC4 inflammasome activation in bone marrow-derived macrophages (BMDMs) is greatly dependent on interferon regulatory factor 8 (IRF8). NLRC4-mediated caspase-1 activation and subsequent production of the inflammasome-dependent cytokines IL-1β and IL-18 and cell death were impaired in IRF8-deficient cells. IRF8 mediated the transcription of genes encoding NAIPs, the receptors for NLRC4 inflammasome, which recognize bacterial flagellin and type III secretion system (T3SS) proteins. IRF8 was critical for host survival following infection with Salmonella Typhimurium or Burkholderia thailandensis. Furthermore, mice deficient in IRF8 were impaired in their ability to produce IL-18 and suffered higher bacterial burdens. Altogether, our data highlights the role of IRF8 as a transcriptional regulator of NAIPs for NLRC4 inflammasome activation.
","abstract_html":"<p>The NLRC4 inflammasome is a crucial part of the innate immune response against bacterial infections. We found that NLRC4 inflammasome activation in bone marrow-derived macrophages (BMDMs) is greatly dependent on interferon regulatory factor 8 (IRF8). NLRC4-mediated caspase-1 activation and subsequent production of the inflammasome-dependent cytokines IL-1β and IL-18 and cell death were impaired in IRF8-deficient cells. IRF8 mediated the transcription of genes encoding NAIPs, the receptors for NLRC4 inflammasome, which recognize bacterial flagellin and type III secretion system (T3SS) proteins. IRF8 was critical for host survival following infection with Salmonella Typhimurium or Burkholderia thailandensis. Furthermore, mice deficient in IRF8 were impaired in their ability to produce IL-18 and suffered higher bacterial burdens. Altogether, our data highlights the role of IRF8 as a transcriptional regulator of NAIPs for NLRC4 inflammasome activation.</p>","abstract_has_math":false,"creators":["Lee, Ein"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Thirumala-Devi Kanneganti, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-05-01T07:00:00Z","date_published":"2019-05-01T07:00:00Z","updated_at":"2026-07-24T05:00:33Z","subjects":["Inflammasome","Interferon regulatory factor","IRF8","NAIP","NLRC4","Salmonella","Medical Immunology","Medical Microbiology","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/465","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Thirumala-Devi Kanneganti, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Lee, Ein"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-01-18T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Inflammasome","Interferon regulatory factor","IRF8","NAIP","NLRC4","Salmonella","Medical Immunology","Medical Microbiology","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/465"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The NLRC4 inflammasome is a crucial part of the innate immune response against bacterial infections. We found that NLRC4 inflammasome activation in bone marrow-derived macrophages (BMDMs) is greatly dependent on interferon regulatory factor 8 (IRF8). NLRC4-mediated caspase-1 activation and subsequent production of the inflammasome-dependent cytokines IL-1β and IL-18 and cell death were impaired in IRF8-deficient cells. IRF8 mediated the transcription of genes encoding NAIPs, the receptors for NLRC4 inflammasome, which recognize bacterial flagellin and type III secretion system (T3SS) proteins. IRF8 was critical for host survival following infection with Salmonella Typhimurium or Burkholderia thailandensis. Furthermore, mice deficient in IRF8 were impaired in their ability to produce IL-18 and suffered higher bacterial burdens. Altogether, our data highlights the role of IRF8 as a transcriptional regulator of NAIPs for NLRC4 inflammasome activation.
"]},{"key":"dc:title","label":"Title","values":["Transcriptional Regulation of NLRC4 Inflammasome by IRF8"]}]}],"canonical_facts":{"dc:contributor":["Thirumala-Devi Kanneganti, Ph.D."],"dc:creator":["Lee, Ein"],"dc:date.available":["2019-01-18T08:00:00Z"],"dc:description.abstract":["The NLRC4 inflammasome is a crucial part of the innate immune response against bacterial infections. We found that NLRC4 inflammasome activation in bone marrow-derived macrophages (BMDMs) is greatly dependent on interferon regulatory factor 8 (IRF8). NLRC4-mediated caspase-1 activation and subsequent production of the inflammasome-dependent cytokines IL-1β and IL-18 and cell death were impaired in IRF8-deficient cells. IRF8 mediated the transcription of genes encoding NAIPs, the receptors for NLRC4 inflammasome, which recognize bacterial flagellin and type III secretion system (T3SS) proteins. IRF8 was critical for host survival following infection with Salmonella Typhimurium or Burkholderia thailandensis. Furthermore, mice deficient in IRF8 were impaired in their ability to produce IL-18 and suffered higher bacterial burdens. Altogether, our data highlights the role of IRF8 as a transcriptional regulator of NAIPs for NLRC4 inflammasome activation.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/465"],"dc:subject":["Inflammasome","Interferon regulatory factor","IRF8","NAIP","NLRC4","Salmonella","Medical Immunology","Medical Microbiology","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences"],"dc:title":["Transcriptional Regulation of NLRC4 Inflammasome by IRF8"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T05:00:33Z"}