Time-resolved dual RNA-Seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection

Streptococcus pneumoniae (pneumococcus) is the main etiological agent of pneumonia. Pneumococcal pneumonia is initiated by bacterial adherence to lung epithelial cells. Infection to the epithelium is a disruptive interspecies interaction involving numerous transcription-mediated processes. Revealing transcriptional changes may provide valuable insights into pneumococcal disease. Dual RNA-Seq allows simultaneous monitoring of the transcriptomes of both host and pathogen. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells by S. pneumoniae and assessed transcriptome changes by dual RNA-Seq. Our data provide new insights into host-microbe interactions and show that the epithelial glutathione-detoxification pathway is activated by bacterial presence. We observed that adherent pneumococci, not free-floating bacteria, access host-associated carbohydrates and repress innate immune responses. In conclusion, we provide a dynamic dual-transcriptomics overview of early pneumococcal infection with easy online access ( http://dualrnaseq.molgenrug.nl ). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies. Graphical Abstract