Although natural killer (NK) cells are considered part of the innate immune system, studies have demonstrated the ability of NK cells to contribute to potent recall responses similar to T and B cells. The precise signals that promote the generation of a long-lived NK cell response are largely undefined. Using cytokine and cytokine receptor deficient mice we investigated the role of the pro-inflammatory cytokine IL-18 on NK homeostasis, activation, expansion, and memory cell formation in response to mouse cytomegalovirus (MCMV) infection. We demonstrate that IL-18 receptor-deficient (IL-18RKO) NK cells exhibit a defect in NK cell expansion following MCMV infection; however, the generation of IL-18RKO memory NK cells was unaffected, as IL-18RKO and wildtype NK cells were detected greater than 5 weeks following MCMV challenge. NK cells deficient in MyD88, the adapter protein which mediates signaling downstream of the IL-1 and IL-18 receptors, also showed a similar defect in expansion. No defect was observed in IL-1RKO NK cells. Interestingly, IL-18RKO NK cells exhibit comparable homeostatic proliferation as wildtype. Thus, these data together highlight the importance of an IL-18-MyD88 signaling axis in NK cell priming, and in the attainment of a robust virus-specific effector NK cell response. Understanding the full contribution of the signals necessary for a protective anti-viral NK cell response will be of interest in the development of vaccines and therapeutics.
- Copyright © 2013 by The American Association of Immunologists, Inc.