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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Secreted Wnt antagonists in scrub typhus.

Thor Ueland1,2,3, Elisabeth Astrup1,4, Kari Otterdal1

  • 1Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.

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Scrub typhus involves altered Wnt signaling with increased Wnt antagonists like SOST, sFRP-3, and WIF-1. This dysregulation is linked to inflammation, organ dysfunction, and poor outcomes in patients.

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Area of Science:

  • Infectious Diseases
  • Immunology
  • Molecular Biology

Background:

  • Mechanisms of inflammation in scrub typhus are not fully understood.
  • Wingless (Wnt) signaling pathways regulate inflammation and infection but haven't been studied in scrub typhus.

Purpose of the Study:

  • Investigate Wnt signaling pathway involvement in scrub typhus.
  • Analyze plasma levels of Wnt antagonists in scrub typhus patients.
  • Correlate Wnt antagonist levels with clinical outcomes and inflammation markers.

Main Methods:

  • Measured plasma levels of DKK-1, sFRP-3, WIF-1, and SOST in scrub typhus patients and controls.
  • Correlated Wnt antagonist levels with inflammation, immune activation, endothelial activation, organ dysfunction, and mortality.
  • Examined Wnt pathway regulation in vitro and ex vivo using gene expression data.

Main Results:

  • Scrub typhus patients showed increased SOST, sFRP-3, WIF-1, and decreased DKK-1 compared to controls.
  • SOST levels correlated positively with monocyte/macrophage activation, endothelial activation, renal dysfunction, and poor outcomes.
  • Canonical Wnt signaling was attenuated in monocytes and mononuclear cells from scrub typhus patients.

Conclusions:

  • Scrub typhus is associated with attenuated Wnt signaling due to dysregulated Wnt antagonists.
  • Elevated SOST levels are linked to renal dysfunction and poor prognosis in scrub typhus.