Host Innate Immune and Metabolic Responses to Microbial Recognition in the Context of Ulcerative Colitis and LPS Signaling

The innate immune system is a crucial part of protecting the body from invading pathogens. The under or overexpression of any aspect in innate immunity can lead to inflammation or autoimmunity. The regulation of protein expression, kinase activity, and cytokine signaling are essential to maintaining a balanced immune response. The goal of this project is to examine different molecular mechanisms that help maintain immune homeostasis to prevent inflammatory diseases but produce effective immune responses when required. First, placenta-specific 8 (PLAC8) expression contributes to intestinal barrier homeostasis and reduces colitis severity. Second, tumor progression locus 2 (TPL2) kinase activity promotes Il1b expression during NLRP3 inflammasome priming. Third, LPS stimulation and type I IFNs alter mitochondrial function through reduced antioxidant gene expression and increased oxidative stress. These studies highlight the different systems utilized by the innate immune system to protect the host and the cellular/molecular mechanisms associated with them. The goal of this work is to show how PLAC8, TPL2, and type I IFNs are pivotal contributors to innate immunity in their specific mechanism.