Fighting the enemy within: Systemic immune defense against mucosal Salmonella infection

Salmonella infection remains a persistent global health threat, as different serovars induce a range of clinical disease, depending upon bacterial virulence and host susceptibility. While some Salmonella serovars induce gastroenteritis in healthy individuals, others can cause more serious systemic enteric fever or invasive nontyphoidal Salmonellosis. The rise of antibiotic resistance, coupled with the absence of effective vaccines for most serovars, perpetuates the spread of Salmonella in endemic regions. A detailed mechanistic understanding of immunity to Salmonella infections has been aided by the availability of mouse models that have served as a valuable tool for understanding host-pathogen interactions under controlled laboratory conditions. These mouse studies have delineated the processes by which early inflammation is triggered after infection, how adaptive immunity is initiated in lymphoid tissues, and the contribution of lymphocyte memory responses to resistance. While recent progress has been made in vaccine development for some causes of enteric fever, deeper understanding of Salmonella-specific immune memory might allow the formation of new vaccines for all serovars. This review will provide a summary of our understanding of vaccination and protective immunity to Salmonella with a focus on recent developments in T cell memory formation.