Dual RNA-seq reveals the complement protein C3-mediated host-pathogen interaction in the brain abscess caused by Staphylococcus aureus.

This study aimed to elucidate the complement protein C3-mediated host-pathogen interaction in the brain abscess caused by Staphylococcus aureus infection. Dual RNA-seq was employed to analyze the transcriptomic differences between C3 deficiency and wild-type mice of S. aureus-induced brain abscess model, and then we investigated the potential regulatory pathways of S. aureus-host interaction mediated by C3 and S. aureus genes associated with the pathogenesis of brain abscess. Finally, C3 deficient-mice and hla mutants of S. aureus were used to verify the specific pathogen-host interaction. In the S. aureus-induced brain abscess mouse model, the transcriptomic analysis revealed significant changes in bacterial virulence factors, such as hemolysin. Based on these data, we predicted a regulatory network formed by genes like hrcA and dnaK, which represent a possible regulation mechanism of S. aureus responding to the host. Furthermore, we identified that hla was the C3 response gene in S. aureus. From the host perspective, we observed that the absence of C3 significantly impacted the host's inflammatory response, primarily by altering the gene expression of several key immune and inflammatory pathways. These findings suggest that C3 deficiency may impair the host's ability to recognize and respond to external pathogens. To the best of our knowledge, this study proposed that S. aureus may affect host immune response through C3, and C3 plays a critical role in regulating inflammation and immune signaling pathways in the brain abscess caused by S. aureus infection.IMPORTANCEIn this work, we employed immunofluorescence and Western blot analysis to reveal a significant upregulation of microglia-derived C3 in the brain abscess mice model caused by S. aureus infection. By integrating the individual RNA sequencing data of S. aureus and the dual RNA-seq data of S. aureus infection brain abscess mice model, the potential regulatory pathways between S. aureus and host were identified, and host C3 not only affects the immune response but also mediates the regulation network of S. aureus. This study provided the potential novel targets for therapeutic strategies in mitigating the effects of S. aureus infections and improving treatment outcomes.