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