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CD8+ T cells induce cachexia during chronic viral infection.

Nat Immunol. 2019 Jun;20(6):701-710. doi: 10.1038/s41590-019-0397-y. | PubMed

Hatoon Baazim1, Martina Schweiger2, Michael Moschinger1, Haifeng Xu3, Thomas Scherer4, Alexandra Popa1, Suchira Gallage5, Adnan Ali5, Kseniya Khamina1, Lindsay Kosack1, Bojan Vilagos1, Mark Smyth1, Alexander Lercher1, Joachim Friske6, Doron Merkler7, Alan Aderem8, Thomas H Helbich6, Mathias Heikenwälder5, Philipp A Lang3, Rudolf Zechner2, Andreas Bergthaler9

  1. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  2. Institute of Molecular Biosciences, University of Graz, Graz, Austria.
  3. Department of Molecular Medicine II, Heinrich Heine University, Düsseldorf, Germany.
  4. Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
  5. Division of Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg, Germany.
  6. Department of Biomedical Imaging and Image-guided Therapy, Division of Gender and Molecular Imaging, Preclinical Imaging Laboratory, Medical University of Vienna, Vienna, Austria.
  7. Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  8. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
  9. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. abergthaler@cemm.oeaw.ac.at.

Abstract

Cachexia represents a leading cause of morbidity and mortality in various cancers, chronic inflammation and infections. Understanding of the mechanisms that drive cachexia has remained limited, especially for infection-associated cachexia (IAC). In the present paper we describe a model of reversible cachexia in mice with chronic viral infection and identify an essential role for CD8+ T cells in IAC. Cytokines linked to cancer-associated cachexia did not contribute to IAC. Instead, virus-specific CD8+ T cells caused morphologic and molecular changes in the adipose tissue, which led to depletion of lipid stores. These changes occurred at a time point that preceded the peak of the CD8+ T cell response and required T cell-intrinsic type I interferon signaling and antigen-specific priming. Our results link systemic antiviral immune responses to adipose-tissue remodeling and reveal an underappreciated role of CD8+ T cells in IAC.

Presented by Hatoon Baazim