CD8+ T cells induce cachexia during chronic viral infection

Baazim, Hatoon; Schweiger, Martina; Moschinger, Michael; Xu, Haifeng; Scherer, Thomas; Popa, Alexandra; Gallage, Suchira; Ali, Adnan; Khamina, Kseniya; Kosack, Lindsay; Vilagos, Bojan; Smyth, Mark; Lercher, Alexander; Friske, Joachim; Merkler, Doron; Aderem, Alan; Helbich, Thomas H; Heikenwälder, Mathias; Lang, Philipp A; Zechner, Rudolf; Bergthaler, Andreas

doi:10.1038/s41590-019-0397-y

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Title		CD8+ T cells induce cachexia during chronic viral infection
Authors		Baazim, Hatoon Schweiger, Martina Moschinger, Michael Xu, Haifeng Scherer, Thomas Popa, Alexandra Gallage, Suchira Ali, Adnan Khamina, Kseniya Kosack, Lindsay Vilagos, Bojan Smyth, Mark Lercher, Alexander Friske, Joachim Merkler, Doron Aderem, Alan Helbich, Thomas H Heikenwälder, Mathias Lang, Philipp A Zechner, Rudolf Bergthaler, Andreas show all authors [1 - 21]
Published in		Nature immunology. 2019, vol. 20, no. 6, p. 701-710
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.
Keywords		Adipose Tissue/diagnostic imaging/immunology/metabolism/virology — Animals — CD8-Positive T-Lymphocytes/immunology/metabolism — Cachexia/diagnostic imaging/etiology/metabolism/pathology — Chronic Disease — Cytokines/blood/metabolism — Female — Interferon Type I/metabolism — Lipid Metabolism — Lipolysis — Lymphocyte Activation/immunology — Lymphocytic choriomeningitis virus — Magnetic Resonance Imaging/methods — Male — Mice — Signal Transduction — Virus Diseases/complications/immunology/virology
Identifiers		DOI: 10.1038/s41590-019-0397-y PMID: 31110314
Full text		Article (Published version) (6 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		La Sclérose en plaques (908)
Projects		H2020: CMIL FP7: LIPOCHEX
Citation (ISO format)		BAAZIM, Hatoon et al. CD8+ T cells induce cachexia during chronic viral infection. In: Nature Immunology, 2019, vol. 20, n° 6, p. 701-710. doi: 10.1038/s41590-019-0397-y https://archive-ouverte.unige.ch/unige:122877