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

Autor:	Webb TJ; Department 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., Carey GB; Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA., East JE; Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA., Sun W; Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA., Bollino DR; Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA., Kimball AS; Department of Microbiology and Immunology, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA., Brutkiewicz RR; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Jazyk:	angličtina
Zdroj:	Pathogens and disease [Pathog Dis] 2016 Aug; Vol. 74 (6). Date of Electronic Publication: 2016 Jun 12.
DOI:	10.1093/femspd/ftw055
Abstrakt:	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. (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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