The endoplasmic reticulum stress-mediated unfolded protein response protects against infection of goat endometrial epithelial cells byTrueperella pyogenesvia autophagy

Abstract

Trueperella pyogenes is an important bacterial pathogen of a wide range of domestic and wild animals. Autophagy plays a key role in eliminating T. pyogenes in a process that is dependent on mechanistic target of rapamycin (mTOR). The endoplasmic reticulum (ER) stress response also is critical for autophagy regulation. However, the relationship between ER stress and T. pyogenes is uncharacterized and the intracellular survival mechanisms of T. pyogenes have not been investigated adequately. In this study, we show that T. pyogenes invades goat endometrial epithelial cells (gEECs). Meanwhile, we observed that GRP78 was upregulated significantly, and that unfolded protein response (UPR) also were activated after infection. Additionally, treatment with activators and inhibitors of ER stress downregulated and upregulated, respectively, intracellular survival of T. pyogenes . Blocking the three arms of the UPR pathway separately enhanced T. pyogenes survival and inflammatory reaction to different levels. We also show that LC3-labeled autophagosomes formed around the invading T. pyogenes and that autolysosome-like vesicles were visible in gEECs using transmission electron microscopy. Moreover, tunicamycin did not inhibit the intracellular survival of T. pyogenes under conditions in which autophagy was blocked. Finally, severe challenge with T. pyogenes induced host cell apoptosis which also may indicate a role for ER stress in the infection response. In summary, we demonstrate here that ER stress and UPR are novel modulators of autophagy that inhibit T. pyogenes intracellular survival in gEECs, which has the potential to be developed as an effective therapeutic target in T. pyogenes infectious disease.

Di(2‐ethylhexyl) phthalate induced thyroid toxicity via endoplasmic reticulum stress: In vivo and in vitro study

“…The results showed that MEHP exposure could increase the level of intracellular Ca 2+ . Moreover, the expression level of chaperone protein GRP78 increased, indicating the dissociation of GRP78 from PERK and IRE1α molecules 38 . After separation from GRP78, phosphorylation of PERK and IRE1α occurs, then activates a series of downstream molecular reactions 39 .…”

“…Moreover, the expression level of chaperone protein GRP78 increased, indicating the dissociation of GRP78 from PERK and IRE1α molecules. 38 After separation from GRP78, phosphorylation of PERK and IRE1α occurs, then activates a series of downstream molecular reactions. 39 Our results showed that the expression of p-PERK and p-IRE1α were significantly increased after MEHP exposure.…”

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