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

Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2252-7. doi: 10.1073/pnas.1222047110. Epub 2013 Jan 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / biosynthesis*
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Killer Cells, Natural / classification
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / microbiology*
  • Killer Cells, Natural / pathology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / microbiology
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology
  • Salmonella typhimurium* / genetics
  • Salmonella typhimurium* / immunology
  • Thy-1 Antigens / metabolism

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Rag2 protein, mouse
  • Thy-1 Antigens
  • RAG-1 protein
  • Interferon-gamma