Fatty acids are crucial to fuel NK cells upon acute retrovirus infection

Simone Schimmer; Daniela Mittermüller; Tanja Werner; Paul E Görs; Sven W Meckelmann; David K Finlay; Ulf Dittmer; Elisabeth Littwitz-Salomon

doi:10.3389/fimmu.2023.1296355

Fatty acids are crucial to fuel NK cells upon acute retrovirus infection

Front Immunol. 2023 Nov 29:14:1296355. doi: 10.3389/fimmu.2023.1296355. eCollection 2023.

Authors

Simone Schimmer¹, Daniela Mittermüller^{1

2}, Tanja Werner¹, Paul E Görs³, Sven W Meckelmann³, David K Finlay⁴, Ulf Dittmer¹, Elisabeth Littwitz-Salomon^{1

5}

Affiliations

¹ Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
² Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg Essen, Essen, Germany.
³ Applied Analytical Chemistry, University of Duisburg-Essen, Essen, Germany.
⁴ School of Biochemistry and Immunology, School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
⁵ Institute for Translational HIV Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Abstract

Natural killer (NK) cells are cytotoxic innate immune cells, able to recognize and eliminate virus-infected as well as cancer cells. Metabolic reprogramming is crucial for their activity as they have enhanced energy and nutritional demands for their functions during an infection. Fatty acids (FAs) represent an important source of cellular energy and are essential for proliferation of immune cells. However, the precise role of FAs for NK cells activity in retrovirus infection was unknown. Here we show that activated NK cells increase the expression of the FA uptake receptor CD36 and subsequently the uptake of FAs upon acute virus infection. We found an enhanced flexibility of NK cells to utilize FAs as source of energy compare to naïve NK cells. NK cells that were able to generate energy from FAs showed an augmented target cell killing and increased expression of cytotoxic parameters. However, NK cells that were unable to generate energy from FAs exhibited a severely decreased migratory capacity. Our results demonstrate that NK cells require FAs in order to fight acute virus infection. Susceptibility to severe virus infections as it is shown for people with malnutrition may be augmented by defects in the FA processing machinery, which might be a target to therapeutically boost NK cell functions in the future.

Keywords: CD36; NK cells; beta-oxidation; cytotoxicity; fatty acids; lipid metabolism; migration; retrovirus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Fatty Acids
Humans
Killer Cells, Natural
Retroviridae Infections*
Retroviridae*

Substances

Fatty Acids

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. EL-S was supported by a grant from the German Research Foundation (DFG) LI 3282/1-1 and LI 3282/2-1. SWM is grateful to the VolkswagenStiftung for funding this work as part of the project LipidDivide: “Resolving the ‘lipid divide’ by unravelling the evolution and role of fatty acid metabolic pathways in Archaea.”