ß2-adrenergic signals downregulate the innate immune response and reduce host resistance to viral infection.
J Exp Med
; 217(4)2020 04 06.
Article
em En
| MEDLINE
| ID: mdl-32045472
ABSTRACT
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 ß2-adrenergic receptor (ß2-AR), which binds the stress mediators adrenaline and noradrenaline, in modulating host response to mouse cytomegalovirus (MCMV) infection. Mice treated with a ß2-AR agonist were more susceptible to MCMV infection. By contrast, ß2-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 ß2-AR signaling could be used to increase resistance to infectious diseases.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Regulação para Baixo
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Receptores Adrenérgicos beta 2
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Infecções por Citomegalovirus
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Imunidade Inata
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article