Salmonella persistence in Mesenteric Lymph Nodes

About This Grant

Project Summary Host-adapted Salmonella enterica strains cause systemic infections and can persist in granulomas within host tissues for extended periods. Often asymptomatic, persistently infected hosts act as crucial reservoirs, silently transmitting the pathogen to new hosts. From a bacterial perspective, maintaining a persistent state is vital for survival in natural settings. Despite this importance, the molecular mechanisms governing Salmonella persistence and host-to-host transmission remain elusive. A clearer understanding of these processes could pave the way for pharmacological eradication of the Salmonella carrier state. Our overarching goal is to unravel how Salmonella enterica serovar Typhimurium (STm) maintains persistence in mammalian tissues, aiming to identify host pathways for preventive and therapeutic innovations. This proposal’s objective is to uncover how STm achieves persistence in mammalian tissues, with the aim of identifying host pathways amenable to preventive and therapeutic strategies. Specifically, we will examine granuloma dynamics and STm survival mechanisms in mesenteric lymph nodes (MLN). The primary objective of this research is to comprehensively characterize dynamics of STm colonization of MLN and to elucidate eosinophil functions that impact pathogen persistence. This will be investigated by examining the interactions between eosinophils and STm, both in vitro and in vivo (Aim 1), and exploring immune-pathogen interactions within distinct MLNs through spatial transcriptomics and immune profiling (Aim 2). Additionally, we aim to characterize the immunoregulatory functions of eosinophils that influence STm persistence in MLNs (Aim 3). Through these efforts, we aim to reveal critical insights into the interplay between host immune pathways and persistent Salmonella infections, informing future strategies to combat chronic bacterial carriage.