First Author | Kupz A | Year | 2013 |
Journal | Proc Natl Acad Sci U S A | Volume | 110 |
Issue | 6 | Pages | 2252-7 |
PubMed ID | 23345426 | Mgi Jnum | J:194337 |
Mgi Id | MGI:5473453 | Doi | 10.1073/pnas.1222047110 |
Citation | Kupz A, et al. (2013) Contribution of Thy1+ NK cells to protective IFN-gamma production during Salmonella Typhimurium infections. Proc Natl Acad Sci U S A 110(6):2252-7 |
abstractText | IFN-gamma is critical for immunity against infections with intracellular pathogens, such as Salmonella enterica. However, which of the many cell types capable of producing IFN-gamma 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)-gammat-dependent lymphocytes, (NK)1.1(+) cells, natural killer T (NKT), and/or B cells alone, replicated the highly susceptible phenotype of IFN-gamma-deficient mice to Salmonella infection. A combination of antibody depletions and adoptive transfer experiments revealed that early protective IFN-gamma was provided by Thy1-expressing natural killer (NK) cells and that these cells improved antibacterial immunity through the provision of IFN-gamma. Further analysis of NK cells producing IFN-gamma 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. |