Location Matters in Defining T Cell–mediated Immunity in Response to Salmonella Typhi Vaccination

nfection with Salmonella enterica serovar Typhi Iresults in nearly 250,000 deaths and more than 21 million illnesses worldwide. S Typhi is transmitted through the fecal-oral route through contaminated food or water and therefore is a major global health problem in regions that lack the infrastructure to provide safe water and ensure adequate sanitation. Of the 2 widely used S Typhi vaccines, Ty21a is an oral live-attenuated vaccine that confers moderate protection against infection for several years. Unfortunately, neither vaccine is suitable for the immunization of young children, one of the primary populations at risk for infection. Furthermore, the emergence of antibiotic-resistant S Typhi underlines the need for the development of the next generation of vaccines. Improved understanding of the mechanisms by which the liveattenuated Ty21a vaccine induces immunity to S Typhi may better inform the development of novel vaccine strategies. To date, the majority of studies regarding T cell–mediated immunity to S Typhi have focused on the characterization of central and effector memory T-cell populations within the peripheral blood of vaccinated individuals, whereas local cellular immunity in the intestinal mucosa has not been characterized. This lack of information regarding activation of mucosal immunity is surprising, considering that the intestine, the terminal ileum in particular, is the initial site of S Typhi infection. Salmonella invades the mucosa through specialized M cells located in Peyer patches, after which myeloid cells take up the bacteria and dendritic cells present Salmonella antigen to T cells. In this issue of Cellular and Molecular Gastroenterology and Hepatology, Booth et al provide a description of ileal immune cell populations in individuals receiving the oral S Typhi Ty21a vaccine. The investigators isolated lamina propria mononuclear cells (LPMCs) from terminal ileum biopsies of volunteers undergoing routine colonoscopies, some of whom were vaccinated with Ty21a 2 weeks prior. To compare peripheral immune cell populations with those in the intestinal mucosa, they also collected peripheral blood (PBMC) immediately before the first vaccine dose (–21 days) and at the time of colonoscopy. Analysis of LPMCs from vaccinated individuals demonstrated that the number of CD8þ T cells expressing gut homing receptors was increased, suggesting that these cells were recruited from the circulation. Furthermore, the authors showed that the mucosal immune response to S Typhi induces the generation of CD8þ effector memory (TEM), central memory (TCM), and CD45RA þ effector memory populations subsets (TEMRA); however, the S Typhi–specific proinflammatory response was distinct and more pronounced within the TEM