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Contribution of Thy1+ NK cells to protective IFN-γ production during Salmonella typhimurium infections.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 Feb 05; Vol. 110 (6), pp. 2252-7. Date of Electronic Publication: 2013 Jan 23. - Publication Year :
- 2013
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 110
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 23345426
- Full Text :
- https://doi.org/10.1073/pnas.1222047110