Date of Award

5-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Microbiology, Immunology, and Biochemistry

Research Advisor

Thirumala-Devi Kanneganti, Ph.D.

Committee

Elizabeth A. Fitzpatrick, Ph.D. David R. Nelson, Ph.D.

Keywords

Inflammasome, Interferon regulatory factor, IRF8, NAIP, NLRC4, Salmonella

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.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

http://orcid.org/0000-0002-9363-5317

DOI

10.21007/etd.cghs.2019.0458

Additional Files
Lee, Ein-Declaration of Authorship.pdf (459 kB)
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