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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
Systemic eosinophil response induced by respiratory syncytial virus
C A Lindemans1, J L L Kimpen, B Luijk
1Department of Pulmonary Diseases, University Medical Centre, Utrecht, the Netherlands.
Insights
Infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) show activated eosinophils, indicating inflammation. These eosinophil changes partially normalize after recovery, suggesting a lasting impact of RSV infection.
Area of Science:
- Immunology
- Pediatrics
- Virology
Background:
- Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease (LRTD) in infants.
- Eosinophils are implicated in LRTD pathogenesis, with inflammation potentially altering granulocyte function.
Purpose of the Study:
- To investigate the activation status of eosinophils in infants with RSV-induced LRTD by analyzing surface marker expression.
- To compare eosinophil activation markers between RSV patients and healthy controls.
Main Methods:
- Analysis of eosinophil surface markers (CD11b, A17, A27, IL-5Ralpha) in 51 infants with RSV LRTD and 10 controls.
- Eosinophils were examined at admission and 6 weeks post-infection, with and without in vitro stimulation (fMLP).
Main Results:
- RSV patients exhibited higher eosinophil CD11b expression compared to controls.
- Priming markers (A17, A27) showed increased expression on stimulated eosinophils from RSV patients, suggesting in vivo priming.
- Interleukin-5 receptor alpha (IL-5Ralpha) expression was down-regulated in RSV patients.
- CD11b remained elevated at follow-up, while other markers normalized.
Conclusions:
- Infants with RSV LRTD have activated peripheral blood eosinophils compared to controls.
- This eosinophil activation state is only partially reversible during convalescence.
- Findings suggest a persistent inflammatory signature in eosinophils following RSV infection.
Abstract:
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease (LRTD) in infants. Eosinophils have been suggested to play a role in the disease pathogenesis of LRTD. Inflammation can induce functional and morphological alterations of peripheral blood granulocytes. In patients with RSV LRTD, we aimed to investigate the eosinophil activation status by analysing surface markers. In vitro stimulation of eosinophils with cytokines leads to up-regulation of CD11b and priming markers recognized by the recently developed priming markers A17 and A27, whereas interleukin (IL)-5Ralpha is being down-regulated. In 51 patients and 10 controls we examined the expression of these surface markers on eosinophils in moderate to severe RSV-induced LRTD patients at the time of admission and 6 weeks later during the convalescence phase. RSV-patients were characterized by a higher eosinophil CD11b expression compared to controls. Although basal A17 and A27 expression was not increased, we observed a significantly higher expression of these priming epitopes on N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated cells of RSV patients compared with cells of controls, indicative of prior in vivo priming. Furthermore, IL-5Ralpha expression was down-regulated on peripheral blood eosinophils of these patients. Follow-up blood samples showed normalization of all markers but CD11b, which was persistently increased. Utilizing cellular markers, we observed that peripheral blood eosinophils from infants with RSV LRTD are in a more activated state compared to eosinophils of controls, which normalizes only partially during convalescence.
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