Crosstalk Network Biomarkers of a Pathogen-Host Interaction Difference Network from Innate to Adaptive Immunity

Crosstalks between host and pathogen are crucial in the infection process. To obtain insight into the defense mechanisms of the host and the pathogenic mechanisms of the pathogen, pathogen-host interactions in the infection process have become a novel and promising research subject in the field of infectious disease. In this study, two pathogen-host dynamic crosstalk networks were constructed to investigate the transition of pathogenic and defensive mechanisms from the innate to adaptive immune system in the entire infection process based on two-sided time course microarray data of C. albicans-zebrafish infection model and database mining. Potential crosstalk network biomarkers for the transition from innate to adaptive immunity were identified based on proteins with larger interaction variations inside the host and pathogen, and at the interface between the host and pathogen. The crosstalk network biomarkers consist of proteins with larger interaction variation scores in the pathogen-host interaction difference network. From the crosstalk network biomarkers, the molecular mechanisms of innate and adaptive immunity were successfully investigated from a systems biology perspective. In view of these results, the proposed crosstalk network biomarkers may serve as potential therapeutic targets of infectious diseases.