Liver Tissue Resident Memory CD4 T cells protect against mucosal Salmonella infection 4634

Abstract Description Salmonella enterica is a gastrointestinal pathogen that causes a variety of intestinal and systemic disease. Vaccine development for systemic Salmonellosis requires understanding of protective mechanisms and the relative importance of mucosal and systemic host responses to bacterial elimination. Here, we examined the relative importance of mucosal and systemic immunity in the control of systemic disease. Delivery of a live attenuated vaccine strain (LVS) by a parenteral route failed to elicit strong mucosal immune responses but was still sufficient to protect against systemic Salmonellosis. One prominent feature of the host response to immunization was the establishment of Salmonella-specific Tissue resident memory (TRM) CD4 T cells in the liver. Adoptive transfer of hepatic TRMs was sufficient to protect mice from challenge infection while TRMs recovered from the intestinal lamina propria (LP) reduced bacterial loads but failed to fully protect. The protective effect of liver and LP TRMs was dependent on expression of IL-18R and the capacity to elicit a non-cognate response in vivo. Overall, these data suggest that a parenteral vaccine that establishes liver TRMs expressing IL-18R will provide robust protection against mucosal and systemic infection with Salmonella. Funding Sources Supported by NIH R01AI139047; T32AI060555. Topic Categories Mucosal and Regional Immunology (MUC)