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Updated: Jun 11, 2025
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
An altered natural killer cell immunophenotype characterizes clinically severe pediatric RSV infection
Roisin B Reilly1, Saïsha K Ramdour1, Mary E Fuhlbrigge1
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Insights
Natural killer (NK) cells are altered in critically ill children with respiratory syncytial virus (RSV) infection. Their immune signature, including frequency and function, correlates with disease severity, suggesting a role in severe pediatric RSV.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) is a major cause of pediatric hospitalizations.
- Immune mechanisms underlying severe pediatric RSV infection remain unclear.
- Natural killer (NK) cells are crucial for innate antiviral immunity.
Purpose of the Study:
- To identify an NK cell immune signature associated with severe pediatric RSV disease.
- To correlate NK cell phenotype and function with clinical severity in critically ill children.
Main Methods:
- Studied 47 critically ill RSV-positive children.
- Analyzed NK cell immunophenotype and cytotoxic function.
- Correlated immune findings with clinical parameters like hypoxemia and ventilation duration.
Main Results:
- Airway NK cells were increased in severe cases, correlating with clinical severity.
- Peripheral NK cells were decreased with altered activating receptor expression (CD69+, NKG2D-).
- Ex vivo, NK cells showed impaired cytotoxicity and aberrant immune synapse function.
Conclusions:
- Altered NK cell frequency and phenotype are associated with severe pediatric RSV.
- NK cells may play a role in RSV immunopathology.
- NK cell immune signature could serve as a biomarker for disease severity.
Abstract:
Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV+ children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV+ children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV+ children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV+ patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV+ patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children.
