An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia

Area of Science:

• Infectious Diseases
• Immunology
• Biomarker Discovery

Background:

• Community-acquired pneumonia (CAP) is frequently caused by Streptococcus pneumoniae.
• Empirical antibiotic therapy for CAP often includes coverage for methicillin-resistant Staphylococcus aureus (MRSA), even when MRSA is not the causative agent.
• Distinguishing between S. pneumoniae and S. aureus pneumonia early can prevent unnecessary antibiotic use.

Purpose of the Study:

• To identify biomarkers capable of differentiating pneumococcal pneumonia from staphylococcal pneumonia.
• To assess the diagnostic potential of these biomarkers in murine models.
• To support pathogen-targeted therapy in CAP patients.

Main Methods:

• Genome-wide transcriptional analysis of lung and peripheral blood in murine models of S. pneumoniae and S. aureus infection.
• Development of prediction models using support vector machine and Monte Carlo cross-validation.
• Validation of identified biomarkers in an independent cohort of mice.

Main Results:

• An interferon signature was identified specifically associated with S. pneumoniae infection.
• Serum concentrations of interferon-induced chemokines CXCL9 and CXCL10 demonstrated high sensitivity, specificity, and predictive power.
• These biomarkers accurately discriminated between S. pneumoniae and S. aureus pneumonia in murine models.

Conclusions:

• Serum CXCL9 and CXCL10 are promising biomarkers for differentiating S. pneumoniae from S. aureus pneumonia.
• These biomarkers can aid in prompt and accurate pathogen-targeted therapy for CAP patients.
• The findings support the use of CXCL9 and CXCL10 as adjunctive diagnostic tools in clinical settings.