Dioscin activates endoplasmic reticulum UPR for defense against pathogen bacteria in Caenorhabditis elegans via IRE-1/XBP-1 pathway.

The unfolded protein response (UPR) is an evolutionarily conserved pathway that senses and responds to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen during bacterial infection. The IRE-1/XBP-1 pathway is a major branch of the UPRER that has been conserved from yeast to human. Dioscin is a steroidal saponin that exhibits a broad spectrum of properties such as anti-oxidant, anti-obesity, hepatoprotective, anti-cancer, anti-viral and anti-inflammatory activities. However, whether the dioscin influences the immune response and the underlying molecular mechanisms remain obscure. We find that 1 μM dioscin increases resistance to the Gram-negative pathogen Pseudomonas aeruginosa PA14. Furthermore, 1 μM dioscin also inhibits the growth of pathogenic bacteria. Meanwhile, dioscin enhances the resistance to pathogens by reducing the bacterial burden in the intestine. Through the genetic screening in C. elegans, we find that dioscin activates the UPRER to promote innate immunity via IRE-1/XBP-1 pathway. Intriguingly, dioscin requires the neural XBP-1 for innate immune response. Our findings suggest that dioscin may be a viable candidate for the treatment of infectious diseases.