Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function.
نویسندگان
چکیده
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 of stress/glucocorticoids, the timing of exposure, the chronology of immunological events, and the underlying mechanisms of this impairment are incompletely understood. In this study, we address each of these questions in the context of a murine cutaneous HSV infection. We show that exposure to stress or corticosterone in only the earliest stages of an HSV-1 infection is sufficient to suppress, in a glucocorticoid receptor-dependent manner, the subsequent antiviral immune response after stress/corticosterone has been terminated. This suppression resulted in early onset and delayed resolution of herpetic lesions, reduced viral clearance at the site of infection and draining popliteal lymph nodes (PLNs), and impaired functions of HSV-specific CD8(+) T cells in PLNs, including granzyme B and IFN-gamma production and the ability to degranulate. In knockout mice lacking glucocorticoid receptors only in T cells, we show that these impaired CD8(+) T cell functions are not due to direct effects of stress/corticosterone on the T cells, but the ability of PLN-derived dendritic cells to prime HSV-1-specific CD8(+) T cells is functionally impaired. These findings highlight the susceptibility of critical early events in the generation of an antiviral immune response to neuroendocrine modulation and implicate dendritic cells as targets of stress/glucocorticoids in vivo. These findings also provide insight into the mechanisms by which the clinical use of glucocorticoids contributes to altered immune responses in patients with viral infections or tumors.
منابع مشابه
Immunity, Implicating Impaired Dendritic Infection Suppress Subsequent Antiviral Earliest Stages of Herpes Simplex Virus-1 Stress-Induced Glucocorticoids at the
متن کامل
The Effect of Hydroalcoholic Extract of Olive Leaves against Herpes Simplex Virus Type 1
Background: It was shown that olive leave extract has antifungal, antibacterial and antiviral activities. The effects of OLE on herpes simplex virus-1 (HSV-1) have not been systematically investigated yet. The aim of this study was to examine the in vitro effect of olive leaf hydroalcoholic extract (OLHE) on HSV-1. Methods: Virucidal effect and viral replication in Vero cell line were studied i...
متن کاملEvaluation of Potential Antiviral Activity of the Hydroalcoholic Extract of Lemon Balm L. against Herpes Simplex Virus Type 1
Background and Aims: Lemon Balm L (Lamiaceae) has been used in a variety of practical applications in medical sciences. Its antiviral activity against herpes simplex virus type-1 (HSV-1) was investigated in cell culture. Lemon Balm hydroalcoholic extract was found to be non-toxic to Vero cells up to concentration 800 ug/ml and inhibited the growth and development of HSV-1 in dose-dependent mann...
متن کاملInhibition of herpes simplex virus type 1 infection by Sambucus ebulus extract in vitro
Background: The emergence of drug-resistant strains of herpes simplex virus type 1 (HSV-1) has been increasingly reported. Therefore, attempts to discover new antiviral agents in particular from natural compounds are required. In this study, we evaluated the possible inhibitory effects of hydroalcoholic extract of Sambucus ebulus (S. ebulus) against HSV-1. Methods: S. ebulus extract was pro...
متن کاملPlasmacytoid Dendritic Cells Contribute to Systemic but Not Local Antiviral Responses to HSV Infections
Plasmacytoid dendritic cells (pDC) produce type I interferons (IFN-I) and proinflammatory cytokines in response to viruses; however, their contribution to antiviral immunity in vivo is unclear. In this study, we investigated the impact of pDC depletion on local and systemic antiviral responses to herpes simplex virus (HSV) infections using CLEC4C-DTR transgenic mice. We found that pDC do not ap...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 184 4 شماره
صفحات -
تاریخ انتشار 2010