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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
Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus
Wouter A A de Steenhuijsen Piters1, Santtu Heinonen2, Raiza Hasrat1
11 Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands.
Insights
The nasopharyngeal bacteria in infants influence respiratory syncytial virus (RSV) disease severity. Specific bacteria like Haemophilus influenzae and Streptococcus are linked to more severe RSV infections, impacting immune responses.
Area of Science:
- Microbiology
- Immunology
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) causes significant infant respiratory infections globally.
- Disease severity in children varies, with risk factors not fully explaining differences.
Purpose of the Study:
- To investigate associations between nasopharyngeal microbiota clusters, host gene expression, and RSV disease severity in young children.
- To understand how the local bacterial ecosystem modulates the immune response to RSV.
Main Methods:
- 16S-rRNA sequencing to profile nasopharyngeal microbiota in children with mild/severe RSV and healthy controls.
- Multivariable analysis of whole-blood transcriptome data to link microbial composition with host response and clinical outcomes.
Main Results:
- Five distinct nasopharyngeal microbiota clusters were identified, enriched with specific bacteria (e.g., H. influenzae, S. aureus).
- Increased H. influenzae and Streptococcus abundance correlated with RSV infection and hospitalization risk.
- RSV infection elevated IFN-related gene expression; H. influenzae/Streptococcus-dominated microbiota amplified TLR and immune cell activation pathways.
Conclusions:
- Nasopharyngeal microbiota composition interacts with RSV infection.
- These interactions may modulate host immune responses, influencing the clinical severity of RSV disease in infants.
Rationale:
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem.
Objectives:
To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.
Methods:
We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity.
Measurements And Main Results:
We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling.
Conclusions:
Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.
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