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Front. Immunol. | doi: 10.3389/fimmu.2018.03020

Natural killer cell education is associated with a distinct metabolic profile

 Caroline Pfeifer1,  Andrew J. Highton2, Sven Peine3, Jürgen Sauter4,  Alexander H. Schmidt4, Madeleine J. Bunders1, 5,  Marcus Altfeld1 and  Christian Körner1*
  • 1Research Department Virus Immunology, Heinrich Pette Institut, Leibniz-Institut für Experimentelle Virologie, Germany
  • 2Research Department Virus Immunology, Heinrich Pette Institut, Leibniz-Institut für Experimentelle Virologie, Germany
  • 3Institut für Transfusionsmedizin, Universitätsklinikum Hamburg-Eppendorf, Germany
  • 4DKMS Life Science Lab GmbH, Germany
  • 5Department of Experimental Immunology and the Emma Children's Hospital, VU University Medical Center, Netherlands

NK cells expressing self inhibitory receptors display increased functionality compared to NK cells lacking those receptors. The acquisition of functional competence in these particular NK cell subsets is termed education. Little is known about the underlying mechanisms that lead to the functional differences between educated and uneducated NK cells. An increasing number of studies suggest that the cellular metabolism is a determinant of immune cell functions. Thus, alterations in cellular metabolic pathways may play a role in the process of NK cell education. Here, we compared the glycolytic profile of educated and uneducated primary human NK cells. KIR-educated NK cells showed significantly increased expression levels of the glucose transporter Glut1 in comparison to NKG2A-educated or uneducated NK cells with and without exposure to target cells. Subsequently, the metabolic profile of NK cell subsets was determined using a Seahorse XF Analyzer. Educated NK cells displayed significantly higher rates of cellular glycolysis than uneducated NK cells even in a resting state. Our results indicate that educated and uneducated NK cells reside in different metabolic states prior to activation. These differences in the ability to utilize glucose may represent an underlying mechanism for the superior functionality of educated NK cells expressing self inhibitory receptors.

Keywords: HLA class I, NK cell metabolism, NK cell education, Glycolysis, GLUT1, killer-cell immunoglobulin-like receptor (KIR), Cytotoxicity

Received: 28 Aug 2018; Accepted: 06 Dec 2018.

Edited by:

Carsten Watzl, Leibniz-Institut für Arbeitsforschung an der TU Dortmund (IfADo), Germany

Reviewed by:

Clair M. Gardiner, Trinity College Dublin, Ireland
Dimitra Peppa, University of Oxford, United Kingdom  

Copyright: © 2018 Pfeifer, Highton, Peine, Sauter, Schmidt, Bunders, Altfeld and Körner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Christian Körner, Heinrich Pette Institut, Leibniz-Institut für Experimentelle Virologie, Research Department Virus Immunology, Hamburg, Hamburg, Germany,