Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses

Tonya J. Webb, Gregory B. Carey, James E. East, Wenji Sun, Dominique R. Bollino, Amy S. Kimball, Randy R. Brutkiewicz

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Natural 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.

Original languageEnglish (US)
Article numberftw055
JournalPathogens and Disease
Volume74
Issue number6
DOIs
StatePublished - Aug 1 2016

Keywords

  • Antigen processing
  • CD1d
  • LCMV
  • Metabolism
  • NKT cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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    Webb, 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), [ftw055]. https://doi.org/10.1093/femspd/ftw055