Studying Innate Immune Responses in Infants With Bronchiolitis

Investigating Type I and Type III Interferon Responses in Infants With Respiratory Syncytial Virus

This study aims to establish whether impaired innate immune responses are associated with severity of Respiratory syncytial virus (RSV) infection.

Respiratory syncytial virus (RSV) causes a spectrum of illness in healthy infants, ranging from asymptomatic infection to life threatening bronchiolitis with respiratory failure. The reasons for the differences in clinical presentation remain unknown. Interferons are natural antiviral factors and components of the innate immune response, which play a role in limiting viral replication.

We postulate that differences in clinical severity of RSV infection may be due to innate immune differences in the production of type I and III interferons (innate interferons). To test this hypothesis, we will recruit infants with mild, moderate and severe RSV bronchiolitis and compare production of innate interferons in blood and respiratory samples, using quantitative and functional analysis. We will determine whether interferon responses differ across a spectrum of clinical severity, and will relate them to viral load.

To establish whether defects in interferon production persist in those infants with severe infection, we will retest them following recovery and measure interferon responses after challenge with live RSV. Demonstrating a persisting defect may suggest a genetically determined defect requiring further investigation. Identification of the mechanisms of severe disease in patients without known risk-factors could lead to targeted therapy to prevent or treat severe disease.

Inclusion Criteria:

• Bronchiolitis
• Infant

Exclusion Criteria:

• Age over 1 year
• Underlying chronic lung disease, prematurity, congenital heart disease