Increased numbers of NKG2C+, NKG2A+, and CD161+ T cells were also associated to HCMV infection. The NKG2C deletion frequency BGJ398 mw was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous

NKG2C+/+ genotype appeared associated with increased absolute numbers of NKG2C+ NK cells. Moreover, HCMV-infected NKG2C+/+ children displayed higher absolute numbers of NKG2A+ and total NK cells than NKG2C+/− individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK-cell compartment in children, revealing a modulatory influence of NKG2C copy number. Human cytomegalovirus (HCMV) infection is highly prevalent worldwide (50–100%), and usually follows a subclinical course in healthy individuals. The virus remains in a lifelong latent state, occasionally undergoing reactivation, but may have a pathogenic GSK1120212 role in immunodeficient and immunosuppressed patients [1-3]. Moreover, HCMV has been associated

with atherosclerosis, lymphoproliferative disorders, and glioblastoma, as well as with an accelerated immunosenescence and a shorter lifespan [4-7]. Vertical transmission of HCMV during pregnancy is considered the most common cause of congenital infection worldwide, affecting ∼0.2–2% of infants and potentially causing fetal lesions [8-10]. Though most infected newborns are asymptomatic, ∼10% display a variety of clinical disorders [8, 11] potentially leading to important

sequelae such as mental retardation and deafness. The type of maternal infection (i.e., primary versus reactivation/reinfection) conditions the risk of congenital infection and the pregnancy stage at which transmission occurs is related to clinical severity [12-16]. Maternal antibodies with neutralizing activity are transferred to the fetus predominantly during the third trimester of gestation and may prevent congenital CMV disease [17]. Wilson disease protein Among other factors, fetal immune immaturity may determine the outcome of congenital infection [18, 19]. An effective defense against HCMV requires the participation of T and NK cells, and the virus has developed different immune evasion strategies [20]. Patients with congenital HCMV infection have been shown to display mature CD8+ T-cell responses [21, 22], and an expansion and differentiation of a specific TcR γδ+ cell subset has been recently reported [23]. In contrast, information on the role of NK cells in this context is rather limited [24, 25]. HCMV infection stably alters the distribution of NK-cell receptors (NKRs) in healthy adult blood donors and children.