| First Author | Wieduwild E | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 4 | PubMed ID | 32045472 |
| Mgi Jnum | J:289099 | Mgi Id | MGI:6432592 |
| Doi | 10.1084/jem.20190554 | Citation | Wieduwild E, et al. (2020) beta2-adrenergic signals downregulate the innate immune response and reduce host resistance to viral infection. J Exp Med 217(4) |
| abstractText | 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 beta2-adrenergic receptor (beta2-AR), which binds the stress mediators adrenaline and noradrenaline, in modulating host response to mouse cytomegalovirus (MCMV) infection. Mice treated with a beta2-AR agonist were more susceptible to MCMV infection. By contrast, beta2-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-gamma production by liver natural killer (NK) cells and stronger resistance to MCMV. However, the control of NK cell IFN-gamma 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 beta2-AR signaling could be used to increase resistance to infectious diseases. |
