PXR as the tipping point between innate immune response, microbial infections, and drug metabolism

Pregnane X receptor (PXR) is a xenosensor that acts as a transcription factor in the cell nucleus to protect cells from toxic insults. In response to exposure to several chemical agents, PXR induces the expression of enzymes and drug transporters that biotransform xenobiotic and endobiotic and eliminate metabolites. Recently, PXR has been shown to have immunomodulatory effects that involve cross-communication with molecular pathways in innate immunity cells. Conversely, several inflammatory factors regulate PXR signaling. This review examines the crosstalk between PXR and nuclear factor kappa B (NFkB), Toll-like receptors (TLRs), and inflammasome components. Discussions of the consequences of these interactions on immune responses to infections caused by viruses, bacteria, fungi, and parasites are included together with a review of the effects of microorganisms on PXR-associated drug metabolism. This paper aims to encourage researchers to pursue studies that will better elucidate the relationship between PXR and the immune system and thus inform treatment development.