Comparative meta-analysis of host transcriptional response during Streptococcus pneumoniae carriage or infection

Infection with Streptococcus pneumoniae causes over 150,000 cases of pneumonia annually in the United States alone. We performed a meta-analysis of publicly available RNA-sequencing data to compare the host-specific intracellular transcriptional responses that differ between infection and carriage with S. pneumoniae in humans and mice. We applied an automated preprocessing workflow to collections of publicly available fastq files that were categorized as either of two phenotypes-infection or carriage in humans and mice. We identified the differentially expressed genes and intracellular signaling pathways that changed in host cells during infection or carriage and whether these human phenotypes could be appropriately modeled at the molecular level in mice. Although we observed multiple differentially expressed genes shared among multiple comparisons, we found no overlapping significant signaling pathways between the mouse and human studies in either phenotype. Based on the samples included in this secondary analysis, we identified a minimal number of generalized transcriptional relationships between host infection and carriage phenotypes of S. pneumoniae that were consistently shared between the mouse and human hosts. Our findings suggest that additional controlled datasets in mouse and human carriage or infection models are needed to better understand the underlying mechanism(s) of invasion and pathogenesis. This knowledge could then contribute to the development of improved prophylactics and/or therapeutics against this pathogen.