CD8+ T cells induce cachexia during chronic viral infection

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / diagnostic imaging
  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Adipose Tissue / virology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cachexia / diagnostic imaging
  • Cachexia / etiology*
  • Cachexia / metabolism
  • Cachexia / pathology
  • Chronic Disease
  • Cytokines / blood
  • Cytokines / 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*
  • Virus Diseases / immunology*
  • Virus Diseases / virology

Substances

  • Cytokines
  • Interferon Type I