CRTAM, an adhesion molecule with immunoregulatory properties, plays a crucial role in late-stage polarization processes, including the localization of proteins like CD44, talin, CD3, and PKC-ζ, as well as the secretion of cytokines such as IFN-γ, IL-17, and IL-22. These processes are essential for the development of memory CD8 T lymphocytes. This study aimed to investigate the impact of CRTAM expression on the generation of memory CD8 T lymphocytes. Our findings demonstrate that CRTAM is indispensable for establishing the CD8 effector memory subpopulation and maintaining CD8 central memory cells long-term after live bacteria immunization. Moreover, during the acute phase of the immune response against an attenuated strain of Salmonella, CRTAM expression promotes a transient KLRG1 + CD127 + phenotype. Furthermore, CRTAM influences protection against virulent Salmonella, impacting the frequency of CD8+ IFN-γ+ and Grz-B+ cells and CD8 T cell retention. Specifically, CRTAM deficiency diminishes the protective capacity and alters the balance of effector and memory CD8 T cell populations. These results collectively establish CRTAM as a crucial regulator of memory CD8 T cell subset dynamic, influencing both the establishment and maintenance of them while also playing a role in the acute and recall response.

Salmonella enterica serovar Typhimurium ( S. Tm) can colonize different intracellular niches, either actively dividing or remaining dormant to persist. Bacterial persisters are phenotypic variants that temporarily enter a non-replicative state. This allows them to evade host cell defenses and antibiotics, leading to chronic infections. We previously reported that during chronic periods, Salmonella remains within B cells in the bone marrow and spleen. However, the dynamics of Salmonella replication and the formation of antibiotic tolerance in infected B cells have not been studied. Here we show that B cells are a favorable reservoir for bacterial persistence. In vitro and in vivo experiments identified non-replicating, persistent Salmonella subsets in splenic B cells. These non-replicative Salmonella are tolerant to antibiotics (cefotaxime and ciprofloxacin), while replicative bacteria remain susceptible. Infected mice demonstrated viable, non-replicative Salmonella in spleen B cells, maintaining antibiotic tolerance. Although acid intravacuolar pH and SPI-2 regulators (SsrA/SsrB) are not necessary for Salmonella persistence in B cells, the SehA/B toxin-antitoxin system facilitates the formation of the persistent phenotype in Salmonella. Overall, we show that B cells are a reservoir for non-replicating, antibiotic-tolerant Salmonella.