학술논문

In Utero Activation of Natural Killer Cells in Congenital Cytomegalovirus Infection
Document Type
article
Source
The Journal of Infectious Diseases. 226(4)
Subject
Paediatrics
Biomedical and Clinical Sciences
Immunology
Perinatal Period - Conditions Originating in Perinatal Period
Infant Mortality
Conditions Affecting the Embryonic and Fetal Periods
Prevention
Vaccine Related
Pediatric Research Initiative
Pediatric
Infectious Diseases
Clinical Research
Aetiology
2.1 Biological and endogenous factors
Infection
Good Health and Well Being
Cytomegalovirus
Cytomegalovirus Infections
Humans
Killer Cells
Natural
Receptors
IgG
NK cells
congenital CMV
cytomegalovirus
CD56-negative NK cells
NKG2C
neonatal immunity
cord blood
flow cytometry
Biological Sciences
Medical and Health Sciences
Microbiology
Biological sciences
Biomedical and clinical sciences
Health sciences
Language
Abstract
BackgroundCongenital cytomegalovirus (CMV) infection is the most common infectious cause of birth defects and neurological damage in newborns. Despite a well-established role for natural killer (NK) cells in control of CMV infection in older children and adults, it remains unknown whether fetal NK cells can sense and respond to CMV infection acquired in utero.MethodsHere, we investigate the impact of congenital CMV infection on the neonatal NK-cell repertoire by assessing the frequency, phenotype, and functional profile of NK cells in cord blood samples from newborns with congenital CMV and from uninfected controls enrolled in a birth cohort of Ugandan mothers and infants.ResultsWe find that neonatal NK cells from congenitally CMV infected newborns show increased expression of cytotoxic mediators, signs of maturation and activation, and an expansion of mature CD56- NK cells, an NK-cell subset associated with chronic viral infections in adults. Activation was particularly prominent in NK cell subsets expressing the Fcγ receptor CD16, indicating a role for antibody-mediated immunity against CMV in utero.ConclusionsThese findings demonstrate that NK cells can be activated in utero and suggest that NK cells may be an important component of the fetal and infant immune response against CMV.Clinical trials registrationNCT02793622.