Open Accessβ2-adrenergic signals downregulate the innate immune response and reduce host resistance to viral infection
Author(s) -
Élisabeth Wieduwild,
Mathilde J.H. Girard-Madoux,
Linda Quatrini,
Caroline Laprie,
Lionel Chasson,
Rafaëlle Rossignol,
Claire Bernat,
Sophie Guia,
Sophie Ugolini
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20190554
Subject(s) - downregulation and upregulation , immune system , biology , immunology , innate immune system , receptor , signal transduction , agonist , cytomegalovirus , virus , microbiology and biotechnology , herpesviridae , viral disease , biochemistry , gene
In humans, psychological stress has been associated with a higher risk of infectious illness. However, the mechanisms by which the stress pathway interferes with host response to pathogens remain unclear. We demonstrate here a role for the β2-adrenergic receptor (β2-AR), which binds the stress mediators adrenaline and noradrenaline, in modulating host response to mouse cytomegalovirus (MCMV) infection. Mice treated with a β2-AR agonist were more susceptible to MCMV infection. By contrast, β2-AR deficiency resulted in a better clearance of the virus, less tissue damage, and greater resistance to MCMV. Mechanistically, we found a correlation between higher levels of IFN-γ production by liver natural killer (NK) cells and stronger resistance to MCMV. However, the control of NK cell IFN-γ production was not cell intrinsic, revealing a cell-extrinsic downregulation of the antiviral NK cell response by adrenergic neuroendocrine signals. This pathway reduces host immune defense, suggesting that the blockade of the β2-AR signaling could be used to increase resistance to infectious diseases.