Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function.

摘要: The systemic elevation of psychological stress-induced glucocorticoids strongly suppresses CD8(+) T cell immune responses resulting in diminished antiviral immunity. However, the specific cellular targets stress/glucocorticoids, timing exposure, chronology immunological events, and underlying mechanisms this impairment are incompletely understood. In study, we address each these questions context a murine cutaneous HSV infection. We show that exposure to stress or corticosterone only earliest stages an HSV-1 infection is sufficient suppress, glucocorticoid receptor-dependent manner, subsequent response after stress/corticosterone has been terminated. This suppression resulted early onset delayed resolution herpetic lesions, reduced viral clearance at site draining popliteal lymph nodes (PLNs), impaired functions HSV-specific cells PLNs, including granzyme B IFN-gamma production ability degranulate. knockout mice lacking receptors cells, not due direct effects on but PLN-derived dendritic prime HSV-1-specific functionally impaired. These findings highlight susceptibility critical events generation neuroendocrine modulation implicate as stress/glucocorticoids vivo. also provide insight into by which clinical use contributes altered patients with infections tumors.