{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:04:21Z","timestamp":1789963461075,"version":"4.0.1"},"reference-count":71,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","award":["24973"],"award-info":[{"award-number":["24973"]}],"id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Natural killer (NK) cells are innate immune cells that eliminate virus\u2010infected and tumour cells by a plethora of signalling pathways, involving the production of cytokines and cytotoxic molecules. NK cell activation and functions demand substantial energy and fatty acids are energy\u2010rich molecules reported to be important for NK cell functions upon viral infections. However, it remains unclear whether NK cells preferentially take up a specific fatty acid. Here, we show in the acute Friend retrovirus infection of mice that linoleic acid (LA) exerts a dual role in modulating NK cells. Interestingly, NK cells increased the uptake of LA upon virus infection in\u00a0vitro and in\u00a0vivo, with higher LA uptake correlating with increased activation of NK cells. While ex\u00a0vivo stimulation with LA increased the expression of cytolytic molecules and subsequently elicited increased target cell killing, it paradoxically decreased the NK cell proliferative capacity, mitochondrial metabolism and increased the cellular stress. To further elucidate the role of LA in\u00a0vivo, we treated mice with exogenous LA during retrovirus infection. While we observed a significant increase of LA levels in the spleen, splenic NK cell activation, cytotoxicity and viral loads were not altered by LA therapy. In addition, we found a decrease in mitochondrial mass and energy levels in NK cells after LA treatment, reflecting its strong effect on mitochondrial metabolism. Our results demonstrate the importance and direct impact of LA for NK cell functions and their metabolic profile. The dual role of LA in enhancing NK cell responses while compromising mitochondrial integrity highlights its potential as a therapeutic adjuvant, alongside other fatty acids, to modulate NK cell functions.<\/jats:p>","DOI":"10.1111\/imm.70205","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:34:42Z","timestamp":1789961682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Linoleic Acid Enhances Murine Natural Killer Cell Function In\u00a0Vitro but Compromises Mitochondrial Bioenergetic Function During Retroviral Infection"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3766-9051","authenticated-orcid":false,"given":"Vaasudevan","family":"Sridhar","sequence":"first","affiliation":[{"name":"Institute for the Research on HIV and AIDS\u2010Associated Diseases University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Schimmer","sequence":"additional","affiliation":[{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Werner","sequence":"additional","affiliation":[{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2973-8715","authenticated-orcid":false,"given":"Rachel","family":"Giesen","sequence":"additional","affiliation":[{"name":"Institute for the Research on HIV and AIDS\u2010Associated Diseases University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Saad","sequence":"additional","affiliation":[{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin P.","family":"Krempe","sequence":"additional","affiliation":[{"name":"Applied Analytical Chemistry University of Duisburg\u2010Essen  Essen Germany"},{"name":"Department of Dermatology University Hospital Essen and German Cancer Consortium  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven W.","family":"Meckelmann","sequence":"additional","affiliation":[{"name":"Applied Analytical Chemistry University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6513-0573","authenticated-orcid":false,"given":"Elisabeth","family":"Littwitz\u2010Salomon","sequence":"additional","affiliation":[{"name":"Institute for the Research on HIV and AIDS\u2010Associated Diseases University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"},{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"17","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells13171464","article-title":"Maintaining the Balance: Regulation of NK Cell Activity","volume":"13","author":"Imsirovic V.","year":"2024","journal-title":"Cells"},{"issue":"2","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/icb.2010.78","article-title":"Activating and Inhibitory Receptors of Natural Killer Cells","volume":"89","author":"Pegram H. 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G.","year":"2023","journal-title":"Biophysical Reviews"},{"issue":"12","key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/s41590-018-0251-7","article-title":"Metabolic Reprogramming of Natural Killer Cells in Obesity Limits Antitumor Responses","volume":"19","author":"Michelet X.","year":"2018","journal-title":"Nature Immunology"},{"issue":"8","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1038\/s42255-025-01330-w","article-title":"The Source of Dietary Fat Influences Anti\u2010Tumour Immunity in Obese Mice","volume":"7","author":"Kunkemoeller B.","year":"2025","journal-title":"Nature Metabolism"},{"issue":"25","key":"e_1_2_9_37_1","doi-asserted-by":"crossref","first-page":"10258","DOI":"10.1073\/pnas.1222404110","article-title":"MYC Inhibition Induces Metabolic Changes Leading to Accumulation of Lipid Droplets in Tumor Cells","volume":"110","author":"Zirath H.","year":"2013","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"14","key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1128\/MCB.25.14.6225-6234.2005","article-title":"Myc Stimulates Nuclearly Encoded Mitochondrial Genes and Mitochondrial Biogenesis","volume":"25","author":"Li F.","year":"2005","journal-title":"Molecular and Cellular Biology"},{"issue":"4","key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s13340-024-00738-1","article-title":"mTORC1 Signaling and Diabetic Kidney Disease","volume":"15","author":"Swaroop V.","year":"2024","journal-title":"Diabetology International"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","DOI":"10.3389\/fvets.2020.00260","article-title":"Oleic and Linoleic Acids Induce the Release of Neutrophil Extracellular Traps via Pannexin 1\u2010Dependent ATP Release and P2X1 Receptor Activation","volume":"7","author":"Alarcon P.","year":"2020","journal-title":"Frontiers in Veterinary Science"},{"issue":"1","key":"e_1_2_9_41_1","doi-asserted-by":"crossref","DOI":"10.1080\/15384047.2024.2325130","article-title":"Linoleic Acid Exhibits Anti\u2010Proliferative and Anti\u2010Invasive Activities in Endometrial Cancer Cells and a Transgenic Model of Endometrial Cancer","volume":"25","author":"Qiu J.","year":"2024","journal-title":"Cancer Biology & Therapy"},{"issue":"1","key":"e_1_2_9_42_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41435-023-00233-8","article-title":"Take My Breath Away\u2010Mitochondrial Dysfunction Drives CD8(+) T Cell Exhaustion","volume":"25","author":"Richter F. 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