Webb, Tonya J.Carey, Gregory B.East, James E.Sun, WenjiBollino, Dominique R.Kimball, Amy S.Brutkiewicz, Randy R.2017-11-212017-11-212016-08Webb, T. J., Carey, G. B., East, J. E., Sun, W., Bollino, D. R., Kimball, A. S., & Brutkiewicz, R. R. (2016). Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses. Pathogens and Disease, 74(6). https://doi.org/10.1093/femspd/ftw055https://hdl.handle.net/1805/14638Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5′-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses.enAttribution 3.0 United StatesCD1dNKT cellsmetabolismArticle