Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense
(A) Heat map of percentile induction of genes induced by treatment of BMDMs with live S. aureus (MOI 10) in wild type (B6), Myd88-/-Trif-/-, or StingGt/Gt mice reveals four distinct clusters of genes. Genes are separated into 4 clusters (I, II, III, and IV) based on mode of induction. (B) Venn diagram demonstrating the breakdown of genes in the four clusters of genes based on >50% dependence on the two main pathways induced. (C) Enriched Jaspar 2016 motifs within promoters of genes within the 4 clusters of genes defined by dependence on TLR and/or STING pathways. (D) GO Biologic Process reveals functions of genes within each cluster. The number of genes listed next to the GO Biologic Process number refers to the number of S. aureus-induced genes in our dataset that contribute to the significant enrichment of the GO term dataset. (E) Comparison of “MyD88/TRIF or STING Independent” cluster of 20 genes with known monocyte/macrophage datasets stimulated with hypoxia reveals significant overlap of signatures (p-value by Fisher's Exact Test).