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Stutte, S.* ; Ruf, J.* ; Kugler, I.* ; Ishikawa-Ankerhold, H.* ; Parzefall, A. ; Marconi, P.* ; Maeda, T.* ; Kaisho, T.* ; Krug, A.* ; Popper, B.* ; Lauterbach, H.* ; Colonna, M.* ; von Andrian, U.* ; Brocker, T.*

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

Brain Behav. Immun. 95, 429-443 (2021)

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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 bodyweight 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Anorexia ; Ghrelin ; Plasmacytoid Dendritic Cells ; Type 1 Interferon ; Viral Infection; Induced Sickness Behavior; Tumor-necrosis-factor; Iifn-producing Cells; Cd8(+) T-cells; Diphtheria-toxin; Food-intake; Hypothalamic Peptide; Gastric Somatostatin; Insulin-secretion; Gene-expression

ISSN (print) / ISBN 0889-1591

e-ISSN 1090-2139

Journal Brain, Behavior and Immunity

Quellenangaben Volume: 95, Pages: 429-443

Publisher Elsevier

Publishing Place Amsterdam [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Experimental Genetics (IEG)

Grants Friedrich Baur-Stiftung
Deutsche Forschungsgemeinschaft