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 Brutkiewicz

Research output: Contribution to journalArticle

10 Citations (Scopus)

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)
JournalPathogens and Disease
Volume74
Issue number6
DOIs
StatePublished - Aug 1 2016

Fingerprint

Natural Killer T-Cells
CD1d Antigen
AMP-Activated Protein Kinases
Antigen Presentation
Innate Immunity
Infection
Lymphocytic choriomeningitis virus
TCF Transcription Factors
Hypoxia-Inducible Factor 1
Metformin
Glycolipids
Deoxyglucose
B-Cell Lymphoma
Glycolysis
Antigen-Presenting Cells
B-Lymphocytes
Pharmacology

Keywords

  • antigen processing
  • CD1d
  • LCMV
  • metabolism
  • NKT cells

ASJC Scopus subject areas

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

Cite this

Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses. / Webb, Tonya J.; Carey, Gregory B.; East, James E.; Sun, Wenji; Bollino, Dominique R.; Kimball, Amy S.; Brutkiewicz, Randy.

In: Pathogens and Disease, Vol. 74, No. 6, 01.08.2016.

Research output: Contribution to journalArticle

Webb, Tonya J. ; Carey, Gregory B. ; East, James E. ; Sun, Wenji ; Bollino, Dominique R. ; Kimball, Amy S. ; Brutkiewicz, Randy. / Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses. In: Pathogens and Disease. 2016 ; Vol. 74, No. 6.
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