Predictive signature of murine and human host response to typical and atypical pneumonia

Area of Science:

• Host-pathogen interactions
• Immunology
• Genomics

Background:

• Clinical differentiation of pneumonia caused by typical bacterial, atypical bacterial, and viral pathogens is challenging.
• Host response-based diagnostics offer a complementary approach to pathogen detection for pneumonia.

Purpose of the Study:

• To develop diagnostic signatures based on host response in murine models of pneumonia.
• To understand and differentiate host responses to typical bacterial, atypical bacterial, and viral pneumonia.
• To validate these signatures in human gene expression data.

Main Methods:

• Murine models were infected with Streptococcus pneumoniae (typical bacterial), Mycoplasma pneumoniae (atypical bacterial), or influenza (viral).
• Peripheral blood gene expression analysis was performed to identify differentially expressed genes.
• Diagnostic signatures were generated and validated in silico using human gene expression datasets.

Main Results:

• Distinct host response signatures were identified for typical bacterial, atypical bacterial, and viral pneumonia.
• Streptococcus pneumoniae infection elicited the most rapid and robust host response.
• Diagnostic signatures achieved high area under the receiver operator curve (auROC) values (0.94-1.00 in mice, 0.82-0.96 in humans).

Conclusions:

• Discrete host responses successfully differentiate pneumonia aetiologies.
• Murine-derived host response signatures demonstrate strong validation in human datasets.
• The conserved nature of host responses across species highlights their diagnostic potential.