ABSTRACT Many pathogens invade host cells and replicate in the protected intracellular niche. The most direct way to counteract this virulence strategy is to kill the afflicted cell by programmed cell death. Pyroptosis is a form of programmed cell death initiated by caspase-1- or -11-driven opening of the gasdermin pore. Although the host cell is killed, we have shown both in vivo and in vitro the intracellular bacteria survive the process of pyroptosis. However, we found that instead of being dispersed into the intracellular space, bacteria within pyroptotic cells become trapped in the torn but mostly intact plasma membrane. Because this trapping is immunologically useful to prevent dissemination, and because the structure of a pyroptotic cell is different than the term debris, we chose to name this structure as a “pore-induced intracellular trap” or PIT. The PIT serves as a nidus for complement deposition, which attracts neutrophils to the PIT. The neutrophils then efferocytose (phagocytosis of a dead cell) the PIT and the bacteria trapped within. Ultimately it is the neutrophil, therefore, that kills the intracellular bacteria. Salmonella Typhimurium has intestinal virulence factors and intracellular virulence factors. In the intestine, it expresses flagellin and invades intestinal epithelial cells using the SPI1 T3SS. Flagellin and SPI1 are readily detected by the NLRC4 inflammasome that activates caspase-1. However, during intracellular replication in macrophages that dominates systemic disease, the bacteria repress flagellin and express the NLRC4-evasive SPI2 T3SS. In order to study pyroptosis in vivo, we engineered the bacteria to express flagellin on demand. In Aim 1 we continue to use this flagellin engineered S. Typhimurium to study PIT clearance mechanisms in vitro and in vivo. Complement is required for clearance of the PIT and its trapped bacteria in vivo. We hypothesize that the reason that complement activates on dead cells is in anticipation that they may retain trapped intracellular bacteria. We investigate the complement initiation pathways that are triggered by the PIT, the importance of C5a and C3a, and the importance of complement opsonization to drive efferocytosis. In Aim 2 we return to wild type S. Typhimurium, asking if the trapping concepts apply to the gastrointestinal phase of infection where these bacteria are detected by NLRC4. We hypothesize that intestinal epithelial cells that exfoliate in response to bacterial invasion also form PITs that trap the bacteria. We further hypothesize that this trapping in the gut lumen is important because it allows infiltrating neutrophils to preferentially target invasive bacteria instead of commensal luminal bacteria. We hypothesize that this is accomplished because invasive bacteria are trapped within the exfoliated intestinal epithelial cells.