PROJECT SUMMARY A successful vaccine for systemic Salmonella infections will need to induce Th1 memory cells, but the tissue location and required functionality of these cells is poorly understood. Our preliminary data show that liver Tissue Resident Memory (TRM) CD4 T cells express higher levels of IL-18R and are more protective than the corresponding TRMs cells in the lamina propria. In this application, we will test, (i) whether IL-18R expression allows non-cognate responsiveness and robust TRM-mediated protection, and (ii) whether the use of a mRNA nanoparticle delivery system can induce this protective population in the liver of vaccinated mice.