Chlamydia psittaci induces GSDME-mediated pyroptosis via the ROS-JNK signaling pathway.

Chlamydia psittaci is an obligate intracellular zoonotic pathogen that causes atypical pneumonia. Pyroptosis is a type of regulated cell death mediated by gasdermin-family proteins and plays an important role in the response to intracellular infection. This study investigates whether C. psittaci infection triggers GSDME-mediated pyroptosis through the ROS-JNK signaling pathway. Our study revealed that infection with C. psittaci induces pyroptosis through caspase-3 activation and subsequent GSDME cleavage in human cervical epithelial (HeLa) cells. Mechanistically, the infection increased intracellular levels of reactive oxygen species (ROS) and phosphorylated c-Jun N-terminal kinase (JNK). Treatment with either the ROS scavenger NAC or the JNK inhibitor SP600125 significantly suppressed pyroptosis. Furthermore, inhibition of either the caspase-3-GSDME axis or the ROS-JNK pathway significantly increased the number of C. psittaci inclusion bodies. Taken together, our findings suggest that the ROS/JNK signaling pathway modulates GSDME-mediated pyroptosis and concurrently restricts C. psittaci replication in host cells, identifying the ROS-JNK-GSDME axis as a key mechanism in C. psittaci-induced pyroptosis. These findings reveal novel therapeutic targets for the treatment of psittacosis.