Type I interferon mediated induction of somatostatin leads to suppression of ghrelin and appetite thereby promoting viral immunity in mice

Susanne Stutte, Janina Ruf, Ina Kugler, Hellen Ishikawa-Ankerhold, Andreas Parzefall, Peggy Marconi, Takahiro Maeda, Tsuneyasu Kaisho, Anne Krug, Bastian Popper, Henning Lauterbach, Marco Colonna, Ulrich von Andrian, Thomas Brocker

Research output: Contribution to journalArticlepeer-review

Abstract

Loss of appetite (anorexia) is a typical behavioral response to infectious diseases that often reduces body weight. Also, anorexia can be observed in cancer and trauma patients, causing poor quality of life and reduced prospects of positive therapeutic outcomes. Although anorexia is an acute symptom, its initiation and endocrine regulation during antiviral immune responses are poorly understood. During viral infections, plasmacytoid dendritic cells (pDCs) produce abundant type I interferon (IFN-I) to initiate first-line defense mechanisms. Here, by targeted ablation of pDCs and various in vitro and in vivo mouse models of viral infection and inflammation, we identified that IFN-I is a significant driver of somatostatin (SST). Consequently, SST suppressed the hunger hormone ghrelin that led to severe metabolic changes, anorexia, and rapid body weight loss. Furthermore, during vaccination with Modified Vaccinia Ankara virus (MVA), the SST-mediated suppression of ghrelin was critical to viral immune response, as ghrelin restrained the production of early cytokines by natural killer (NK) cells and pDCs, and impaired the clonal expansion of CD8+ T cells. Thus, the hormonal modulation of ghrelin through SST and the cytokine IFN-I is fundamental for optimal antiviral immunity, which comes at the expense of calorie intake.

Original languageEnglish
Pages (from-to)429-443
Number of pages15
JournalBrain, Behavior, and Immunity
Volume95
DOIs
StatePublished - Jul 2021

Keywords

  • Anorexia
  • Ghrelin
  • Plasmacytoid dendritic cells
  • Type 1 interferon
  • Viral infection

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