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

Cui Xiao1, Canming Hu1, Zhe Liu1

  • 1Department of public health laboratory sciences, School of public health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Insights

Chlamydia psittaci infection triggers pyroptosis, a cell death process, via the ROS-JNK signaling pathway and GSDME activation. This pathway also limits bacterial replication, offering potential therapeutic targets for psittacosis.

Area of Science:

  • Cell Biology
  • Immunology
  • Microbiology

Background:

  • Chlamydia psittaci causes atypical pneumonia and is an obligate intracellular zoonotic pathogen.
  • Pyroptosis, a programmed cell death, is crucial for combating intracellular infections.

Purpose of the Study:

  • To investigate if C. psittaci infection induces GSDME-mediated pyroptosis via the ROS-JNK signaling pathway.
  • To explore the role of this pathway in C. psittaci replication.

Main Methods:

  • Infection of human cervical epithelial (HeLa) cells with C. psittaci.
  • Assessing pyroptosis markers (caspase-3 activation, GSDME cleavage).
  • Measuring reactive oxygen species (ROS) and phosphorylated JNK (JNK) levels.
  • Utilizing ROS scavenger (NAC) and JNK inhibitor (SP600125).

Main Results:

  • C. psittaci infection activated caspase-3 and cleaved GSDME, inducing pyroptosis.
  • Infection elevated intracellular ROS and phosphorylated JNK levels.
  • NAC and SP600125 treatments suppressed pyroptosis.
  • Inhibiting the caspase-3-GSDME axis or ROS-JNK pathway increased C. psittaci inclusion bodies.

Conclusions:

  • The ROS/JNK signaling pathway modulates GSDME-mediated pyroptosis in C. psittaci infection.
  • This pathway restricts C. psittaci replication in host cells.
  • The ROS-JNK-GSDME axis is a key mechanism in C. psittaci-induced pyroptosis, revealing potential therapeutic targets for psittacosis.