Contribution of Thy1(+) NK cells to protective IFN-gamma production during Salmonella Typhimurium infections

Kupz, A; Scott, TA; Belz, GT; Andrews, DM; Greyer, M; Lew, AM; Brooks, AG; Smyth, MJ; Curtiss, R; Bedoui, S; Strugnell, RA

Author(s): Kupz, A; Scott, TA; Belz, GT; Andrews, DM; Greyer, M; Lew, AM; Brooks, AG; Smyth, MJ; Curtiss, R; Bedoui, S; Strugnell, RA;
Details: Publication Year 2013-02-05,Volume 110,Issue #6,Page 2252-2257
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
Abstract: 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)-gamma t-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 inresponse 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.
Publisher: NATL ACAD SCIENCES
Keywords: NATURAL-KILLER-CELLS; ENTERICA SEROVAR TYPHIMURIUM; T-CELLS; ACQUIRED-RESISTANCE; ORAL CHALLENGE; LISTERIA-MONOCYTOGENES; VIRULENT SALMONELLAE; INITIAL SUPPRESSION; ADAPTIVE IMMUNITY; ADOPTIVE TRANSFER
Research Division(s): Molecular Immunology; Immunology
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568339/
Publisher's Version: https://doi.org/10.1073/pnas.1222047110

Creation Date: 2013-02-05 12:00:00