Research Article: Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster

Date Published: February 21, 2018

Publisher: Public Library of Science

Author(s): Choon Kwan Kim, Youn Mi Choi, Eunsin Bae, Mihn Sook Jue, Hyung Seok So, Eung-Soo Hwang, Graciela Andrei.


The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

Partial Text

Herpes zoster (HZ) results from reactivation of the latent varicella-zoster virus (VZV) after a primary VZV infection. Several risk factors for HZ have been identified to date, such as older age, depressed cell-mediated immunity (CMI), diabetes, genetic susceptibility, trauma, recent psychological stress, female gender and European ethnicity [1]. Although the role of adaptive immunity in HZ pathogenesis has been well investigated, the role of innate immunity has not. Reduced VZV-specific CMI is the most important risk factor for HZ [2–4], with VZV-specific effector T cell activity peaking at 1–3 weeks after the onset of HZ and decreasing rapidly thereafter [5]. Because natural killer (NK) cells also play important roles in the early stage of viral infection [6], NK cell activity might affect the pathogenesis of HZ. Although NK cell activity varies with age and gender among healthy individuals, only small variations are observed over a long period of time in each individual, and individuals have been subdivided into consistently high and low groups [7]. By comparing NK cell activity between patients with a recent HZ diagnosis and control subjects without a history of HZ, we aimed to investigate the possible role of NK cells in the pathogenesis of HZ.

Due to the major role of T cell-mediated adaptive immunity in HZ pathogenesis, studies of the role of NK cells in HZ have been very limited. Following elucidation of the complex mechanism of NK cell activation in the past few decades [17], studies examining the associations between the activity of NK cells and diseases were performed using recent technical advances for measuring NK cell activity [18,19]. In contrast to general concepts of NK cell activation during viral infection, we observed low levels of IFN-γ secretion from NK cell of patients with HZ compared with controls without a history of HZ. Our findings are supported by the results of two previous studies of NK cell activity in patients with HZ: NK cell cytotoxicity was reduced during HZ infection in immunocompromised hosts [20], and IFN-γ production by peripheral blood mononuclear cells (PBMCs) was decreased during the early stages of HZ infection [21]. Based on these findings, VZV activates the immune system and simultaneously uses several immune evasion mechanisms to limit NK cell activity. VZV infection was recently shown to modulate the expression of a ligand for the natural killer group 2D (NKG2D), a potent NK cell-activating receptor [22,23]. After VZV is reactivated in the dorsal ganglion and skin, the overall activity of NK cells from peripheral blood might be reduced through the modulation of NKG2D expression. However, we are unable to determine whether low levels of IFN-γ secretion from NK cell was a predisposing factor for HZ or secondary consequence of the immunomodulatory effects of VZV in the present study. Multiple sequential tests over a long period are required in the same patients with HZ to clarify the change in NK cell IFN-γ secretion after VZV reactivation.




0 0 vote
Article Rating
Notify of
Inline Feedbacks
View all comments