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

• Published in: BMJ open respiratory research 2024-08, Vol.11 (1), p.e002001
• Main Authors: McCravy, Matthew, O’Grady, Nicholas, Khan, Kirin, Betancourt-Quiroz, Marisol, Zaas, Aimee K, Treece, Amy E, Yang, Zhonghui, Que, Loretta, Henao, Ricardo, Suchindran, Sunil, Ginsburg, Geoffrey S, Woods, Christopher W, McClain, Micah T, Tsalik, Ephraim L
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacterial Infection; Bacterial infections; Disease Models, Animal; Female; Females; Gender; Gene expression; Gene Expression Profiling; Host-Pathogen Interactions; Humans; Infectious diseases; Influenza; Laboratories; Mice; Mice, Inbred C57BL; Mycoplasma pneumoniae - genetics; Mycoplasma pneumoniae - isolation & purification; Original Research; Orthomyxoviridae Infections - immunology; Pathogens; Pneumonia; Pneumonia, Bacterial - diagnosis; Pneumonia, Bacterial - microbiology; Pneumonia, Mycoplasma - diagnosis; Pneumonia, Pneumococcal - microbiology; Pneumonia, Viral - diagnosis; Pneumonia, Viral - immunology; Respiratory Infection; ROC Curve; Sensitivity and Specificity; Streptococcus infections; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - isolation & purification; Viral infection; Viral infections
• ISSN: 2052-4439; 2052-4439
• DOI: 10.1136/bmjresp-2023-002001

BackgroundPneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection.MethodsWe used murine models of typical bacterial, atypical bacterial and viral pneumonia to develop diagnostic signatures and understand the host’s response to these types of infections. Mice were intranasally inoculated with Streptococcus pneumoniae, Mycoplasma pneumoniae, influenza or saline as a control. Peripheral blood gene expression analysis was performed at multiple time points. Differentially expressed genes were used to perform gene set enrichment analysis and generate diagnostic signatures. These murine-derived signatures were externally validated in silico using human gene expression data. The response to S. pneumoniae was the most rapid and robust.ResultsMice infected with M. pneumoniae had a delayed response more similar to influenza-infected animals. Diagnostic signatures for the three types of infection had 0.94–1.00 area under the receiver operator curve (auROC). Validation in five human gene expression datasets revealed auROC of 0.82–0.96.DiscussionThis study identified discrete host responses to typical bacterial, atypical bacterial and viral aetiologies of pneumonia in mice. These signatures validated well in humans, highlighting the conserved nature of the host response to these pathogen classes.