Changes in whole heart gene expression resulting from endothelial TLR2 deletion

We report the application of bulk RNA sequencing for profiling changes in mouse cardiac lysates as a result of changes in innate immunity function. We generated an inducible endothelial cell toll-like receptor 2 knockout and assessed changes in overall gene expression in the absence of pathogen presence. We find that over 200 genes are differentially regulated between the two genotypes that are solely due to the presence of endogenous signaling within these animals. We also show that the genes that are differentially regulated are tied to the immunity function of the endothelium and that removal of toll-like receptor 2 signaling creates a diminished response by the immune system to wound healing and tumor development. Finally, we demonstrate that other immunomodulatory pathways are further affected, suggesting that changes outside of the endothelium are driven by endothelial-toll-like receptor 2 signaling. This study provides a framework for the application of tissue specific knockouts and profiling the role of endothelial as an innate immunity organ.