Contribution of Thy1+ NK cells to protective IFN-γ production during Salmonella Typhimurium infections.

IFNi is critical for immunity against infections with intracellular pathogens. such as Salmonella enterica. However, which of the many cell types capable of producing IFN-γ controls Salmonella infections remains unclear. Using a mouse model of systemic Salmonella infection, we observed that only a lack of all lymphocytes or CD90 (Thy1)+ cells, but not the absence of T cells, Retinoic acid-related orphan receptor (ROR)-γt-dependent lymphocytes, (NK)1.1+ cells, natural killer T (NKT), andlor B cells alone, replicated the highly susceptible phenotype of IFN-γ-deficient mice to Salmonella infection. A combination of antibody depletions and adoptive transfer experiment revealed that early protective IFNγ was provided by Thy1-expressing natural killer (NK) cells and that these cells improved antibacterial immunity through the provision of IFN-γ Further analysis of NK cells producing IFN-γ in responseto Salmonella indicated that less mature NK cells were more efficient at mediating antibacterial effector function than terminally differentiated NK cells. Inspired by recent reports of Thy1+ NK cells contributing to immune memory, we analyzed their role in secondary protection against otherwise lethal WT Salmonella infections. Notably, we observed that a newly generated Salmonella vaccine strain not only conferred superior protection compared with conventional regimens but that this enhanced efficiency of recall immunity was afforded by incorporating CD4-CD8-Thy1+ cells into the secondary response. Taken together, these findings demonstrate that Thy1-expressing NK cells play an important role in antibacterial immunity. [ABSTRACT FROM AUTHOR]