CHARACTERIZING SALMONELLA TYPHIMURIUM'S EVASION OF INNATE IMMUNITY

Inflammasomes play an important role in defense against infection. The NOD-like Receptors CARD Domain Containing 4 (NLRC4) inflammasome detects the Type Three Secretion System (T3SS) system rod and needle proteins, leading to caspase-1 activation. Active caspase-1 induces pro-interleukin-1β (pro-IL-1β) and pro-IL-18 maturation and pyroptosis, a lytic form of cell death. Pyroptosis clears infected cells by exposing the mature cytokines, drawing the attention of neutrophils which phagocytose the dead, infected cells. Salmonella Typhimurium uses two distinct T3SS, namely Salmonella Pathogenicity Island 1 (SPI-1) and SPI-2, to infect macrophages. Prior in vitro data suggests that NLRC4 detects rod and needle proteins composing the T3SS in SPI-1, however it is unclear if SPI-2 rod and needle proteins are detected as well. Because of the similarity across pathogenicity islands, we hypothesized that the rod and needle proteins that form the T3SS in SPI-2 are also detected by NLRC4. We show that the SPI-2 needle protein, SsaG, is detected by NLRC4 in vitro while the SPI-2 rod protein, SsaI, evades detection in vitro. This is demonstrated via a retrovirus lethality assay and a dose-dependent relationship through protein transfections followed by Enzyme-Linked Immunosorbent Assays (ELISAs) and western blot. Although our data strongly suggests the SPI-2 needle protein is detected in vitro, it remains unclear why Salmonella Typhimurium phenotypically evades inflammasome detection in vivo while simultaneously expressing the detectable SsaG.Bachelor of Scienc