Exploring innate immune signaling pathways leading to IL-6 production in bone marrow macrophages infected with Francisella tularensis 9381

Abstract Description Francisella tularensis (F.t) is a highly infectious bacterium and causative agent of tularemia disease, as it causes an overproduction of pro-inflammatory cytokines such as interleukin-6 (IL-6). The inflammatory response is driven by pattern recognition receptors (PRRs) which then detect pathogen-associated molecular patterns (PAMPs) alongside damage-associated molecular patterns (DAMPs). Interferon regulatory factors (IRFs), particularly IRF3 and IRF7, play a key role in regulating these responses. The objective behind this study is to better understand the contributions of IRF3 and IRF7 in the production of IL-6 when infected with F.t. Through immortalized bone marrow macrophages derived from C57BL/6 wild-type mice, as well as IRF3, IRF7, and IRF3/7 double knockout cell lines, a standard infection protocol was implemented, followed by an enzyme-linked immunosorbent assay (ELISA) to quantify cytokine production. Additionally, techniques of flow cytometry and pico cell imaging were utilized to analyze macrophage responses, such as cell death activation with fluorescent antibody markers and cell staining. Preliminary results demonstrate reduced IL-6 production within the knockout cell lines compared to controls, showcasing their importance as transcription factors in macrophage response to F.t. infection. Future directions include expanding inhibitor studies through phagocytosis assays to investigate the role of specific inflammasome pathways. Funding Sources Research in this project was supported by the National Research of General Medical Sciences of NIH under the fellowship grant number #T34GM145529. The content is solely the responsibility of the authors and does not necessarily represent the official views of funding agencies of the National Institutes of Health. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)