2. Academic Validation
  3. NK cell-derived IFNγ mobilizes free fatty acids from adipose tissue to promote early B cell activation during viral infection

NK cell-derived IFNγ mobilizes free fatty acids from adipose tissue to promote early B cell activation during viral infection

  • Nat Metab. 2025 May;7(5):985-1003. doi: 10.1038/s42255-025-01273-2.
Mia Krapić # 1,  Inga Kavazović # 1,  Sanja Mikašinović 1,  Karlo Mladenić 1,  Fran Krstanović 2,  Gönül Seyhan 3,  Sabine Helmrath 3,  Elena Camerini 4,  Ilija Brizić 2,  Fleur S Peters 4,  Marc Schmidt-Supprian 3,  Bojan Polić 1,  Tamara Turk Wensveen 5 6,  Felix M Wensveen 7
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 2 Center for proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 3 Institute for Experimental Hematology, Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University Munich, Munich, Germany.
  • 4 Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
  • 5 Center for Diabetes, Endocrinology and Cardiometabolism, Thalassotherapia Opatija, Opatija, Croatia.
  • 6 Department of Internal Medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 7 Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. felix.wensveen@uniri.hr.
  • # Contributed equally.
PMID: 40217117 DOI: 10.1038/s42255-025-01273-2
Abstract

The immune system plays a major role in the regulation of adipose tissue homeostasis. Viral Infection often drives fat loss, but how and why this happens is unclear. Here, we show that visceral adipose tissue transiently decreases adiposity following viral Infection. Upon pathogen encounter, adipose tissue upregulates surface expression of ligands for activating receptors on natural killer cells, which drives IFNγ secretion. This cytokine directly stimulates adipocytes to shift their balance from lipogenesis to lipolysis, which leads to release of lipids in circulation, most notably of free fatty acids. The free fatty acid oleic acid stimulates early-activated B cells by promoting Oxidative Phosphorylation. Oleic acid promoted expression of co-stimulatory B7 molecules on B cells and promoted their ability to prime CD8+ T cells. Inhibiting lipid uptake by activated B cells impaired CD8+ T cell responses, causing an increase of viral replication in vivo. Our findings uncover a previously unappreciated mechanism of metabolic adaptation to Infection and provide a better understanding of the interactions between immune cells and adipose tissue in response to inflammation.

Figures
Products