Natural Killer Cell Deficiencies in a Consecutive Series of Children with Herpetic Encephalitis

Abstract

Natural killer (NK) cells play a fundamental role in innate and early phases of adaptive immunity against viral infections, both in humans and in animal models. To date, NK cell deficiencies in patients with severe herpetic infections have been reported in single cases, and their role as predisposing factor is still controversial. Five children affected by herpetic encephalitis were consecutively admitted to the Anna Meyer Children's Hospital in Florence (Italy) between 2003 and 2005. We therefore investigated the presence of NK cell deficiencies in a consecutive series of children with herpetic encephalitis. Five healthy children were included in the study as controls. Differential WBC counts, main Ig and IgE class serum analysis, cytofluorimetric analysis of circulating T, B and NK cells were performed on our study population. Sequencing of a selected region of CD16A gene transcript was carried out in two patients. All patients resulted to be affected by deficiencies related to NK cells in respect to controls. One patient was also affected by lymphopenia, while no other significant deficits of immunity were detected in the study population. To date, this is the first survey that demonstrates isolated NK cell deficiencies in a cohort of consecutive patients affected by severe herpes simplex infections. These findings suggest a role for NK cell deficiencies as a predisposing factor for increased susceptibility and severe course of disease in these patients.

NK Cells in Central Nervous System Disorders

“…Shortly after they were discovered, NK cells were shown to play an important role in antiviral immune responses. The rare patients completely devoid of NK cells were extremely susceptible to infections by viruses of the herpes family (26,27). Five consecutive children with herpetic encephalitis were shown to have functional NK cell deficiencies (27).…”

“…The rare patients completely devoid of NK cells were extremely susceptible to infections by viruses of the herpes family (26,27). Five consecutive children with herpetic encephalitis were shown to have functional NK cell deficiencies (27). By using a mouse model of HSV1 encephalitis, Adler et al (28) directly demonstrated that NK cells have an important role in the defense against this severe form of infection.…”

Pseudorabies Virus US3 Protein Kinase Protects Infected Cells from NK Cell-Mediated Lysis via Increased Binding of the Inhibitory NK Cell Receptor CD300a

“…For herpesviruses in particular, functional NK cells are crucial for limiting virus spread and disease symptoms. Indeed, impaired NK cell activity has been associated with life-threatening encephalitis caused by the human alphaherpesviruses herpes simplex virus 1 (HSV-1) and varicellazoster virus (VZV) (2)(3)(4). Given the strong antiviral potential of NK cells against herpesviruses in particular, it comes as no surprise that several herpesvirus strategies for evading NK cells have been discovered (5).…”

Modulation of CD112 by the alphaherpesvirus gD protein suppresses DNAM-1–dependent NK cell-mediated lysis of infected cells

“…Functional NK cells are of particular importance in preventing herpesviruses from causing aggravated disease, including life-threatening encephalitis for alphaherpesviruses like HSV and varicella-zoster virus (1)(2)(3). The significance of the NK cell response against herpesviruses is also reflected by the various mechanisms that these pathogens have evolved to evade or delay it (4).…”