Vibrio cholerae porin OmpU induces LPS tolerance by attenuating TLR-mediated signaling

Sanica C Sakharwade1, Arunika Mukhopadhaya1

  • 1Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Sector 81, SAS Nagar, Manauli, 140306 Punjab, India.

Molecular Immunology
|October 12, 2015
PubMed

Insights

Vibrio cholerae OmpU porin suppresses lipopolysaccharide (LPS)-mediated immune responses by attenuating Toll-like receptor (TLR) signaling. OmpU pretreatment inhibits pro-inflammatory cytokine production and enhances macrophage phagocytosis.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Porins, like Vibrio cholerae OmpU, are pathogen-associated molecular patterns recognized by the host immune system.
  • V. cholerae OmpU enhances bacterial survival but exhibits complex immunomodulatory effects, including both pro-inflammatory and anti-inflammatory actions.

Purpose of the Study:

  • To investigate the impact of OmpU pretreatment on lipopolysaccharide (LPS)-mediated immune responses.
  • To elucidate the molecular mechanisms by which OmpU modulates Toll-like receptor (TLR) signaling pathways.

Main Methods:

  • Treatment of RAW 264.7 mouse macrophage cells and human peripheral blood mononuclear cells (PBMCs) with OmpU followed by LPS stimulation.
  • Analysis of M2 polarization, TLR2/TLR6 signaling, MyD88 and IRAK recruitment, NFκB translocation, IRAK-M expression, IL-10 production, TNFα levels, phagocytosis, and co-stimulatory molecule expression.

Main Results:

  • OmpU pretreatment did not induce M2 polarization of macrophages/monocytes.
  • OmpU attenuated LPS-mediated TLR2/TLR6 signaling by reducing TLR-MyD88-IRAK complex formation and NFκB nuclear translocation.
  • OmpU upregulated IRAK-M expression, partially involved IL-10 in down-regulating LPS-induced TNFα production, enhanced phagocytosis, and reduced co-stimulatory molecule expression.

Conclusions:

  • OmpU suppresses LPS-mediated immune responses by attenuating the TLR signaling pathway.
  • OmpU exhibits immunomodulatory functions impacting macrophage polarization, cytokine production, and phagocytic activity.

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