a PCA plot illustrates murine lung response to the pneumococcal strains. Interestingly, host transcriptional response to rafR swap in blood isolate (4559M, light purple) is similar to the murine response to the original ear strain (9–47-Ear, dark orange). b Differential gene expression of transcriptional response to pneumococcal ear and blood isolates shows a widespread transcriptional rewiring. Specifically, 433 genes are activated in response to infection by ear isolate (9–47-Ear) while 787 genes are activated (FC > 1.5, p < 0.05) by blood isolate (4559-Blood). c–e Specific gene ontology terms are enriched in differentially expressed host genes in response to pneumococcal infection: cytokine–cytokine receptor interaction (c), interleukin-17 signaling pathway (d), and necroptosis (e). A: comparison between 9–47-Ear to 9–47M; B: 9–47-Ear to 4559-Blood; C: 9–47-Ear to 4559M; D: 9–47M to 4559-Blood; E: 9–47M to 4559M and F: 4559-Blood to 4559M. Asterisk (*) denotes statistically significant functional enrichment for the indicated strain–strain comparison.