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

Tonya J Webb1, Gregory B Carey2, James E East2

  • 1Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA twebb@som.umaryland.edu.

Pathogens and Disease
|June 15, 2016
PubMed

Insights

Metabolic changes in cells can enhance the presentation of antigens to Natural Killer T (NKT) cells, potentially improving innate immune responses against infections and cancers.

Area of Science:

  • Immunology
  • Metabolic pathways
  • Cellular metabolism

Background:

  • Natural Killer T (NKT) cells are crucial for innate immunity.
  • CD1d-mediated antigen presentation to NKT cells is known, but recognition mechanisms for infected/cancerous cells are unclear.
  • 5'-AMP-activated protein kinase (AMPK) regulates lipogenesis and may signal danger to NKT cells.

Purpose of the Study:

  • To investigate how metabolic alterations affect CD1d-mediated antigen presentation to NKT cells.
  • To explore the role of AMPK activation in NKT cell responses during infection and malignancy.
  • To assess if targeting cellular metabolism can induce innate immune responses.

Main Methods:

  • Examined CD1d-mediated antigen presentation following lymphocytic choriomeningitis virus infection.
  • Assessed antigen-presenting cells pretreated with metabolic inhibitors (2-deoxyglucose, cobalt chloride, AICAR, metformin) to induce Hypoxia Inducible Factors (HIF) and activate AMPK.
  • Evaluated NKT cell responses to malignant B cells and B-cell lymphomas expressing HIF-1α.

Main Results:

  • Lymphocytic choriomeningitis virus infection increased CD1d-mediated antigen presentation.
  • Pharmacological agents inhibiting glycolysis, inducing HIF, and activating AMPK significantly enhanced NKT cell activation.
  • NKT cells showed preferential responses to malignant B cells, which express HIF-1α.

Conclusions:

  • Altering cellular metabolism can enhance CD1d-mediated antigen presentation to NKT cells.
  • Targeting cellular metabolism represents a novel strategy for inducing innate immune responses against infections and cancers.
  • AMPK activation and HIF induction are key mediators in this metabolic immune signaling.
Keywords:
CD1dLCMVNKT cellsantigen processingmetabolism

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