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Pseudomonas aeruginosa Mediates Host Necroptosis through Rhl-Pqs Quorum Sensing Interaction

Zihao Liu1,2, Lu Sun3, Lupeng Li4,5,6,7

  • 1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH.

Immunohorizons
|September 23, 2024
PubMed

Insights

Pseudomonas aeruginosa quorum sensing (QS) regulates host cell death. A deficiency in the rhl QS system increases macrophage necroptosis, mediated by the pqs system, revealing a key cross-talk during infection.

Area of Science:

  • Microbiology
  • Immunology
  • Cell Biology

Background:

  • Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen.
  • Bacterial quorum sensing (QS) regulates virulence and host interactions.
  • The role of P. aeruginosa QS in host programmed cell death remains unclear.

Purpose of the Study:

  • To investigate the role of P. aeruginosa QS in host programmed cell death.
  • To elucidate the specific QS systems involved in P. aeruginosa-induced cell death.

Main Methods:

  • Utilized P. aeruginosa mutants deficient in QS systems (rhl, pqs).
  • Assessed macrophage cell death and necroptosis markers (RIPK3, MLKL phosphorylation) in vitro and in vivo.
  • Analyzed the interplay between rhl and pqs QS systems.

Main Results:

  • Mice bone marrow macrophage cell death increased in P. aeruginosa rhl-deficient infections.
  • Elevated RIPK3 and MLKL phosphorylation indicated heightened necroptosis.
  • Upregulation of the pqs QS system by the rhl deficiency caused necroptosis.
  • Deletion of pqs in rhl-deficient P. aeruginosa abolished macrophage necroptosis.

Conclusions:

  • P. aeruginosa QS significantly influences host necroptosis.
  • The rhl-pqs QS axis mediates P. aeruginosa-induced macrophage necroptosis.
  • Highlights cross-talk between bacterial QS and host immune pathways.

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