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            Cytomegalovirus (CMV) infection, here in humans. In red and green the Natural  Killer cells are trying to spawn a way to the infected cell. © Inserm /  Jabrane-Ferrat, Nabila 
            When stress weakens the immune system
            PRESS RELEASE |  05 MARCH 2020 - 11:55 AM | BY INSERM (PRESS ROOM) IMMUNOLOGY, INFLAMMATION,  INFECTIOLOGY AND MICROBIOLOGY 
             In recent years, several studies have linked psychological stress to reduced  immune defenses, but the mechanisms at stake remained ill-defined. Sophie  Ugolini, Inserm research director at Center d'Imunologie de Marseille-Luminy,  and colleagues from CNRS and AixMarseille University have just shown that this  association between stress and immunity is largely mediated by a type of  receptor that binds to stress hormones, the β2-adrenergic receptor. Their  results are published in the Journal of Experimental Medicine. 
            
            For several years, the scientific community has been  interested in the effects of psychological stress on health. Studies have shown  that in case of infection, stress is associated with reduced efficiency of the  immune defense system. With his team, Sophie Ugolini, Inserm research director  at the Center for Immunology de Marseille-Luminy (Inserm / CNRS / Aix-Marseille  Université), sought to explain the association biologically. Researchers expressed  interest in receptors on the surface of many cells in the body (including cells  which are specific to stress hormones, adrenaline and noradrenaline:  β2-adrenergic receptors. 
            The researchers then assessed the animals' resistance to infection  in the absence of these receptors. For this, they exposed to cytomegalovirus  from mice genetically engineered to be free of β2-adrenergic receptors. In  these animals, the stress hormones could no longer attach to β2 receptors and  therefore could no longer act. These mice were much more resistant to viral  infection (90% survival against only 50% for control mice). These initial  results therefore suggest that stimulation of β2-adrenergic receptors by stress  hormones would responsible for weakening the immune system under psychological  stress. 
            Towards new therapeutic avenues
            To better understand the mechanisms involved, the team also analyzed the response  immune system of mice lacking β2-adrenergic receptors. She observed an increase  in the production of inflammatory cytokines, molecules produced by immune cells  and promoting the elimination of viruses. 
            The researchers notably discovered that the β2-adrenergic  receptors particularly inhibit the response of certain immune cells, Natural  Killer cells (NK). Stimulated by stress hormones, β2- receptors adrenergic  block these Natural Killers from producing a particular type of cytokine required  to allow virus removal. 
            "We have experimentally confirmed that the stress  hormones that bind to β2-adrenergic receptors reduce the immune response and  decrease in the production of certain inflammatory cytokines, required for  virus removal, says Sophie Ugolini. "According to the researcher, this  work could open therapeutic perspectives. "By targeting the β2- receptor adrenergic,  it would indeed be possible, in certain pathological contexts, to remove the  immune brakes caused by a state of stress," Sophie Ugolini concluded.  
            Sources
            β2-adrenergic signals downregulate the innate immune  response and reduce host resistance to viral infection 
            Elisabeth  Wieduwild1 , Mathilde Girard-Madoux1 , Linda Quatrini1,2, Caroline Laprie1 ,  Lionel Chasson1 , Rafaëlle Rossignol1 , Claire Bernat1 , Sophie Guia1 , and  Sophie Ugolini 
            1  Aix Marseille Univ, CNRS, INSERM, CIML, Centre d'Immunologie de  Marseille-Luminy, Marseille, France  
              2  Department of Immunology, IRCSS Bambino Gesù Children's Hospital, Rome, Italy 
            Journal  of Experimental Medicine: https://doi.org/10.1084/jem.20190554 
              Researcher Contact 
              Sophie Ugolini 
              Inserm Research Director 
              Team leader "Innate lymphoid cells and Neural  Regulation of Immunity" 
              Unit 1104 - Marseille Center for Immunology - Luminy  (CIML) 
              +33 (0) 4 91 26 94 44 
              ugolini@ciml.univ-mrs.fr  
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