(A) Host cell survival after Spn supernatant exposure, shown by confocal microscopy using a LIVE (green)/DEAD (magenta) stain. Scale bar: 20 μm. (B and C) Host cell survival after mucin-, glycan-, or monosaccharide-treated (MS-treated) Spn supernatant exposure, measured by AlamarBlue. (D and E) MUC5AC and glycan exposure triggers transcriptional changes in Spn TIGR4 at 5 hours (average FC from three biological replicates). (F and G) RT-qPCR quantification of ply gene expression after 5 hour exposure to mucin isoforms (F) and in multiple Spn strains (G). (H) IL-1β release upon Spn-neutrophil interaction, measured by ELISA. (I) Neutrophil phagocytosis of GFP-tagged Spn TIGR4, with or without mucins, measured by flow cytometry. (J and K) Lung and blood bacterial burden in mice infected with mucin-treated Spn. n = 10/group. (B, C, F–K) Data represent mean ± SEM with biological replicates shown. (B, C, H) Mann-Whitney U test; (F) Wilcoxon test; (J–K) Kruskal-Wallis test with Dunn’s correction; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.