Chlamydia trachomatis modulation of host inflammasome

Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide with approximately 90 million new cases reported annually. Complications to infection in women include pelvic inflammatory disease, ectopic pregnancy and increased risk of cervical cancer. Despite these significant medical concerns there are fundamental gaps in our understanding of Chlamydia pathogenesis, particularly with regards to the host immune response and inflammasome activation. C. trachomatis is known to stimulate IL-1beta secretion and activate the NLRP3 inflammasome but the mechanism of modulation is not known. Our strong preliminary data demonstrates that a Chlamydial protein, CT226, interacts with Leucine Rich Repeat Protein 1 (LRRFIP1), and Flightless 1 (FLII), upstream regulators of the NLRP3 inflammasome. We hypothesize that this interaction between CT226 and LRRFIP1/FLII modulates inflammasome activation during C. trachomatis infection. With the latest innovative genetic tools and transformation methods, we have generated a CT226 deletion strain of C. trachomatis. The CT226 deletion mutant will be assessed for differences in inflammasome activation, secretion of 1L-1beta, IL-18 and caspase 1 activation. Using siRNA depletion and inflammasome deficient cell lines we will assess the role of inflammasome activation on C. trachomatis replication, infectivity and intracellular survival. The proposed research is critical to understanding the role inclusion membrane proteins have in host immune response during C. trachomatis infections and will address a key fundamental knowledge gap regarding Chlamydia modulation of inflammasome activation. Project Number: 1R03AI185821-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Erika Lutter | Institution: OKLAHOMA STATE UNIVERSITY STILLWATER, STILLWATER, OK | Award Amount: $145,745 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 IIDA-M (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R03AI18582101A1