YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro
Transcriptional cofactors YAP/TAZ have recently been found to support
autophagy and inflammation, which are part of cell-autonomous immunity
and are critical in antibacterial defense. Here, we studied the role of YAP
against Staphylococcus aureus using CRISPR/Cas9-mutated HEK293 cells and a
primary cell-based organoid model. We found that S. aureus infection increases
YAP transcriptional activity, which is required to reduce intracellular S.
aureus replication. A 770-gene targeted transcriptomic analysis revealed that
YAP upregulates genes involved in autophagy/lysosome and inflammation
pathways in both infected and uninfected conditions. The YAP-TEAD transcriptional
activity promotes autophagic flux and lysosomal acidification,
which are then important for defense against intracellular S. aureus. Furthermore,
the staphylococcal toxin C3 exoenzyme EDIN-B was found effective in
preventing YAP-mediated cell-autonomous immune response. This study
provides key insights on the anti-S. aureus activity of YAP, which could be
conserved for defense against other intracellular bacteria.