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Acanthamoeba proteases contribute to macrophage activation through PAR1 , but not PAR2

Antonella Cano1, Antonella Mattana2, Fiona L Henriquez3

  • 1Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK.

Parasite Immunology
|December 23, 2018
PubMed
Abstract

Insights

Acanthamoeba proteases stimulate macrophage IL-12 production via protease-activated receptor 1 (PAR1), but not PAR2. IL-6 production is independent of both PAR1 and PAR2, offering insights into Acanthamoeba infections.

Area of Science:

  • Immunology
  • Parasitology
  • Cell Biology

Background:

  • Acanthamoeba infections trigger a strong innate immune response involving macrophages.
  • Acanthamoeba protease production is a key factor in virulence.

Purpose of the Study:

  • Investigate the role of Acanthamoeba trophozoite proteases in stimulating interleukin-12 (IL-12) and interleukin-6 (IL-6) production.
  • Determine the involvement of protease-activated receptors (PAR1 and PAR2) on murine macrophages in response to Acanthamoeba proteases.

Main Methods:

  • Utilized protease inhibitors (leupeptin, E64) to assess protease activity.
  • Employed specific antagonists for PAR1 and bone marrow-derived macrophages from PAR2 gene-deficient mice to evaluate receptor involvement.
  • Measured IL-12 and IL-6 cytokine production by macrophages.

Main Results:

  • Acanthamoeba proteases stimulate IL-12 and IL-6 production by murine macrophages.
  • PAR1, but not PAR2, is crucial for Acanthamoeba-induced IL-12 production.
  • Acanthamoeba-induced IL-6 production is independent of both PAR1 and PAR2.

Conclusions:

  • This study demonstrates, for the first time, the involvement of PARs on macrophages in the immune response to Acanthamoeba.
  • Findings provide valuable insights into the mechanisms of Acanthamoeba infections.
  • Potential implications for developing novel therapeutic strategies against Acanthamoeba infections.
Keywords:
AcanthamoebaPAR1PAR2cytokinesmacrophagesprotease-activated receptorsproteases

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