Pro-Inflammatory Cytokines Control The Anti-Viral Nk Cell Response.

dc.contributor.advisorSun, Joseph
dc.contributor.authorMadera, Sharline
dc.description.abstractAlthough natural killer (NK) cells are considered part of the innate immune system, recent studies have demonstrated the capability of virus-specific NK cells to become long-lived and 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. This dissertation investigates the role of pro-inflammatory cytokines interleukin (IL)-12, IL-18, and type I IFN on the NK cell response during mouse cytomegalovirus (MCMV) infection. We demonstrate that IL-12 and its signaling component STAT4 are indispensible for MCMV-specific NK cell expansion and generation of “memory” NK cells in lymphoid and non-lymphoid tissues. Furthermore, IL-12 and STAT4 signaling in activated NK cells increased the expression of the adaptor protein MyD88, which mediates signaling downstream of the IL-18 receptor, and T-box transcription factor T-bet. During MCMV infection, NK cells required IL-18 receptor and MyD88 for optimal primary expansion, but not recall responses. In addition, NK cell-specific deletion of T-bet or Eomes crippled the anti-viral NK cell response. Lastly, we show type I IFN and STAT1 signaling protects NK cells form NKG2D-mediated killing, thus promoting a robust antiviral NK cell response. This work highlights the complex, non-redundant, and stage-specific role of pro-inflammatory cytokines and transcription factors on the NK cell response.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.subjectnatural killer cells
dc.subjectpro-inflammatory cytokines
dc.subjectT-box transcription factors
dc.subjectviral infection
dc.titlePro-Inflammatory Cytokines Control The Anti-Viral Nk Cell Response.
dc.typedissertation or thesis & Microbial Pathogenesis Cornell Graduate School of Medical Sciences of Philosophy


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