Kupz, Andreas, Scott, Timothy A., Belz, Gabrielle T., Andrews, Daniel M., Greyer, Marie, Lew, Andrew M., Brooks, Andrew G., Smyth, Mark J., Curtiss, Roy, Bedoui, Sammy, and Strugnell, Richard A. (2013) Contribution of Thy1+ NK cells to protective IFN-γ production during Salmonella Typhimurium infections. Proceedings of the National Academy of Sciences of the United States of America, 110 (6). pp. 2252-2257.

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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.

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