IL-18-MyD88 signaling axis is important in the attainment of a robust virus-specific effector NK cell response but dispensable for memory formation (P1248)

Abstract

Abstract 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.