University of Tennessee Health Science Center
Transcriptional Regulation of NLRC4 Inflammasome by IRF8
Abstract
dc:description.abstract<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>
Degree
thesis:*- Name thesis:degree_name
- Master of Science (MS)
- Level thesis:degree_level
- Thesis
- Discipline thesis:degree_discipline
- Biomedical Sciences
- Year dc:date.available
- 2019
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Lee, Ein
- Contributors dc:contributor
-
- Thirumala-Devi Kanneganti, Ph.D.
Subjects
dc:subject × 11Identifiers
dc:identifier.*- Repository record dc:identifier
- https://dc.uthsc.edu/dissertations/465
- OAI identifier oai:identifier
- oai:dc.uthsc.edu:dissertations-1465