Helicobacter pylori PldA modulates TNFR1-mediated p38 signaling pathways to regulate macrophage responses for its

Wei Yang Sit1, Mei-Ling Cheng2, Tsan-Jan Chen1

  • 1Institute of Molecular and Cellular Biology & Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.

Gut Microbes
|October 6, 2024
PubMed

Insights

Helicobacter pylori phospholipase A (PldA) disrupts macrophage immune responses, aiding bacterial survival and antibiotic resistance. Inhibiting PldA offers a promising therapeutic strategy against H. pylori infections.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Helicobacter pylori is a major cause of gastrointestinal diseases.
  • Increasing antibiotic resistance in H. pylori poses a significant clinical challenge.

Purpose of the Study:

  • To investigate the role of H. pylori phospholipase A (PldA) in host immune modulation.
  • To identify PldA as a potential therapeutic target against H. pylori.

Main Methods:

  • Studied the effect of PldA on macrophage membrane lipids and signaling pathways.
  • Assessed the impact of PldA inhibition on H. pylori viability and host cell survival.
  • Conducted in vivo studies to evaluate PldA's role in bacterial persistence and immune response.

Main Results:

  • PldA incorporates lysophosphatidylethanolamine into macrophage membranes, disrupting bilayer structure.
  • PldA impairs TNFR1-mediated p38-MK2 signaling, reducing autophagy and increasing apoptosis in macrophages.
  • Pharmacological inhibition of PldA reduced H. pylori viability and enhanced macrophage survival.
  • In vivo studies confirmed PldA's essential role in H. pylori persistence and immune cell recruitment.

Conclusions:

  • H. pylori PldA is critical for immune evasion by modulating host macrophage membranes via TNFR1 signaling.
  • PldA is a key virulence factor and a promising therapeutic target for combating H. pylori infections, including multidrug-resistant strains.

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