Vibrio cholerae OmpU Mediates CD36-Dependent Reactive Oxygen Species Generation Triggering an Additional Pathway of

G V R Krishna Prasad1, Vinica Dhar1, Arunika Mukhopadhaya2

  • 1Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, 140306 Punjab, India.

Insights

Vibrio cholerae porin OmpU triggers inflammatory responses via TLR2 and CD36 receptors. Macrophages use both, while monocytes rely solely on TLR2, explaining macrophages

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • OmpU is a porin from Gram-negative bacteria Vibrio cholerae.
  • OmpU is known to induce inflammatory cytokine production in human and mouse monocytes and macrophages via TLR1/2-MyD88-NF-κB signaling.

Purpose of the Study:

  • To investigate the mechanisms underlying OmpU-induced inflammatory responses in monocytes and macrophages.
  • To identify the specific signaling pathways and receptors involved in OmpU recognition.

Main Methods:

  • Cell culture of human and mouse monocytes and macrophages.
  • Stimulation with purified OmpU protein.
  • Analysis of MAPK (p38, JNK) activation.
  • Assessment of reactive oxygen species (ROS) generation.
  • Investigation of Toll-like receptor 2 (TLR2) and CD36 involvement.
  • Confocal microscopy for OmpU translocation studies.

Main Results:

  • OmpU induces p38 and JNK MAPK activation in both monocytes and macrophages.
  • In macrophages, p38 activation is TLR2-dependent, while JNK activation involves ROS from NADPH oxidase and mitochondria.
  • OmpU-mediated mitochondrial ROS may involve OmpU translocation to mitochondria.
  • NADPH oxidase-mediated ROS production is linked to CD36 activation, identifying OmpU as a novel CD36 ligand.
  • In monocytes, both JNK and p38 activation are solely TLR2-dependent.

Conclusions:

  • Macrophages utilize both TLR2 and CD36 to recognize OmpU, leading to potent proinflammatory responses.
  • Monocytes primarily rely on TLR2 for OmpU recognition.
  • The differential receptor usage by macrophages and monocytes contributes to the heightened inflammatory capacity of macrophages.

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