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


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.

Test our anti-stress technology for free

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.


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:
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

Test our anti-stress technology for free