Host Respiratory Transcriptome Signature Associated with Poor Outcome in Children with Influenza-Staphylococcus...

Area of Science:

• Microbiology
• Immunology
• Genomics

Background:

• Influenza and Staphylococcus aureus coinfection, particularly with methicillin-resistant S. aureus (MRSA), leads to severe, often fatal, disease in pediatric patients.
• Understanding the molecular mechanisms of this coinfection is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To identify host and pathogen transcriptomic signatures in the respiratory tract of critically ill children with influenza-S. aureus coinfection (ISAC).
• To determine if these signatures can predict worse clinical outcomes.

Main Methods:

• Messenger RNA (mRNA) was extracted from endotracheal aspirate samples of pediatric patients.
• Evaluated S. aureus virulence genes and host gene expression profiles.
• Compared transcriptomic data between patients with different coinfection statuses and clinical outcomes.

Main Results:

• While influenza-MRSA coinfection showed worse outcomes, only 6 of 190 S. aureus virulence genes were differentially expressed between MRSA and methicillin-susceptible S. aureus coinfections, with no predictive value for outcome.
• Patients with poor outcomes (death or prolonged dysfunction) exhibited reduced expression of interferons and down-regulation of interferon γ-induced immune cell chemoattractants (CXCL10 and CXCL11).
• Host airway gene expression profiles, not pathogen profiles, predicted worse clinical outcomes in ISAC.

Conclusions:

• Host transcriptomic signatures in the airway are key predictors of clinical outcomes in pediatric influenza-S. aureus coinfection.
• Reduced expression of specific host immune genes, including interferons and related chemokines, is associated with severe disease and poor prognosis in ISAC.