Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior syndrome by reprogramming inflammatory monocytes to produce IL-10.
Sickness behavior syndrome (SBS) as characterized by fatigue and depression impairs quality of life in patients with inflammatory diseases caused by infections and autoimmunity. Systemic engagement of CD40 in mice leads to an inflammatory syndrome with acute hepatitis, lymphadenopathy and development of SBS as evidenced by induction of sleep and weight loss. In the study presented here we show that the elimination of resident tissue macrophages in mice by antibody-mediated neutralization of colony-stimulating factor-1 receptor (CSF1R) did not prevent CD40 induced hepatitis, but conferred resistance to the development of SBS. The protective effect of CSF1R mAb on weight loss and behavior changes induced by CD40 activation coincided with the transformation of pro-inflammatory monocytes to IL-10 producing myeloid cells. In IL-10 knockout mice CSF1R neutralization failed to exert protection from the occurrence of SBS. This study establishes the unexpected key role of CSF1R in the polarization of inflammatory monocytes and thereby SBS in inflammatory liver diseases.
Institute of Experimental Immunology, University of Zurich, Switzerland.
Andreas Felix
AF
Müller
Institute of Experimental Immunology, University of Zurich, Switzerland.
Laura
L
Strauss
Institute of Experimental Immunology, University of Zurich, Switzerland.
Melanie
M
Greter
Department of Neurology, Inselspital, University Hospital Berne, Switzerland.
Heidemarie
H
Gast
Immunodeficiency Clinic, Department Biomedicine, University Hospital Basel, Switzerland.
Mike
M
Recher
Institute of Experimental Immunology, University of Zurich, Switzerland.
Burkhard
B
Becher
Institute of Experimental Immunology, University of Zurich, Switzerland. Electronic address: fontana.adriano7@gmail.com.
Adriano
A
Fontana
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology; D055809:Illness Behavior / Q000187:drug effects / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009043:Motor Activity / Q000276:immunology
D057134:Antibodies, Neutralizing; D019013:CD40 Antigens; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor
Macrophage polarization; Macrophage-colony stimulating factor; Microglia; Sleep; Wasting syndrome