NF-κB/ROS and ERK pathways regulate NLRP3 inflammasome activation in Listeria monocytogenes infected BV2 microglia

Lin Yuan1,2, Yurong Zhu1,3, Shuang Huang1

  • 1School of Medicine, Jiangsu University, Zhenjiang, 212013, P. R. China.

Insights

Listeria monocytogenes triggers neuroinflammation via NLRP3 inflammasome activation in microglia. Inhibiting this pathway, along with NF-κB and ERK signaling, reduces pyroptosis and IL-1β secretion, offering therapeutic insights.

Area of Science:

  • Neuroscience
  • Immunology
  • Microbiology

Background:

  • Listeria monocytogenes is a food-borne pathogen causing potentially lethal neurolisteriosis, particularly in immunocompromised individuals.
  • Microglia are the primary targets of L. monocytogenes within the central nervous system (CNS), but the mechanisms driving neuroinflammation are not fully understood.

Purpose of the Study:

  • To investigate the role of the NLRP3 inflammasome in L. monocytogenes-induced neuroinflammation in microglia.
  • To elucidate the involvement of NF-κB and ERK signaling pathways in this process.

Main Methods:

  • Experiments utilized the BV2 microglial cell line and a murine model of L. monocytogenes infection.
  • Pharmacological inhibition of the NLRP3 inflammasome, NF-κB, and ERK pathways was employed.
  • Assays measured pyroptosis, caspase-1 activation, IL-1β secretion, and ROS production.

Main Results:

  • L. monocytogenes infection activated pyroptosis and the NLRP3 inflammasome in BV2 microglia.
  • Inhibition of the NLRP3 inflammasome significantly reduced L. monocytogenes-induced pyroptosis.
  • Inhibition of NF-κB and ERK pathways decreased caspase-1 activation and IL-1β secretion, indicating their role in NLRP3 inflammasome activation.

Conclusions:

  • The NLRP3 inflammasome is critically involved in L. monocytogenes-induced neuroinflammation and reactive oxygen species (ROS) production.
  • ERK and NF-κB signaling pathways are essential for the activation of the NLRP3 inflammasome during L. monocytogenes infection, both in vitro and in vivo.

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