1. Contribution of Thy1+ NK cells to protective IFN-γ production during Salmonella typhimurium infections.
- Author
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Kupz A, Scott TA, Belz GT, Andrews DM, Greyer M, Lew AM, Brooks AG, Smyth MJ, Curtiss R 3rd, Bedoui S, and Strugnell RA
- Subjects
- Adoptive Transfer, Animals, Cell Differentiation immunology, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, DNA-Binding Proteins immunology, Homeodomain Proteins genetics, Homeodomain Proteins immunology, Interferon-gamma deficiency, Interferon-gamma genetics, Killer Cells, Natural classification, Killer Cells, Natural pathology, Lymphocyte Subsets immunology, Lymphocyte Subsets microbiology, Lymphocyte Subsets pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Salmonella Infections, Animal microbiology, Thy-1 Antigens metabolism, Interferon-gamma biosynthesis, Killer Cells, Natural immunology, Killer Cells, Natural microbiology, Salmonella Infections, Animal immunology, Salmonella typhimurium genetics, Salmonella typhimurium immunology
- Abstract
IFN-γ 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), and/or B cells alone, replicated the highly susceptible phenotype of IFN-γ-deficient mice to Salmonella infection. A combination of antibody depletions and adoptive transfer experiments revealed that early protective IFN-γ 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 response to 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.
- Published
- 2013
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