Abstract Body: Background: Streptococcus pneumoniae (Spn) remains the leading cause of community-acquired pneumonia (CAP). As many as 30% of patients hospitalized for CAP experience a major adverse cardiac event (MACE). Importantly, the elevated risk for MACE is not only limited to the time of acute infection but also extends several years post-hospitalization.
Research Question: Is the host response to Spn-mediated injury in the heart different from the response to sterile injury?
Goals: To identify defining features of the host response to Spn in the heart via differences in gene expression.
Methods: We performed a bioinformatic analysis of bulk RNAseq data collected from hearts of mice acutely infected with Spn and compared this to publicly available data sets of mice that received experimental myocardial infarction, i.e. ischemia reperfusion and permanent ligation. Using DeSeq2, we identified 2,971 genes with differential expression between the infected and infarcted conditions. To identify gene expression differences that might be relevant to human patients, we subsequently used the Reactome GSA software to map our differential expression results onto predicted human pathways.
Results: Categorization of the gene roles identified those in the classical antibody-mediated complement activation as the dominant pathway with differential expression. Reactome analysis of the top 5 differentially expressed genes (p < 0.05) at the individual level identified BAIAP2L1, CXCL9, IRF7, IL18BP, RPL12, and PSMB10 as significantly upregulated in Spn infected hearts versus infarcted hearts. As one feature of Spn mediated damage is the recruitment of immune cells to the affected sites and cardiac remodeling, we validated upregulation of CXCL9 as well as CXCL10, potent recruiters of T-cells, as enhanced during Spn infection.
Conclusions: Our analyses provide information on how the host response to disseminated pneumococcal infection in the heart is distinct from sterile injury and identified mediators that may be contributing to adverse cardiac remodeling.