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

Antonella Cano, Antonella Mattana, Fiona L. Henriquez, James Alexander, Craig W. Roberts

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Abstract

AIM Acanthamoeba infections are characterized by an intense localized innate immune response associated with an influx of macrophages. Acanthamoeba protease production is known to affect virulence. Herein, the ability of Acanthamoeba trophozoite proteases, of either the laboratory Neff strain, or a recently isolated clinical strain, to stimulate IL-12 and IL-6 and to activate protease-activated receptors, PAR1 and PAR2 expressed on murine macrophages, was investigated.
METHOD AND RESULTS Using selected protease inhibitors, leupeptin and E64, we showed that Acanthamoeba proteases can stimulate IL-12 and IL-6 by murine macrophages. Subsequently, using specific antagonists to inhibit PAR1, and bone-marrow derived macrophages from PAR2 gene deficient mice, we demonstrate that PAR1, but not PAR2 contributes to macrophage IL-12 production in response to Acanthamoeba. In contrast, Acanthamoeba-induced IL-6 production is PAR1 and PAR2 independent.
CONCLUSION This study shows for the first time the involvement of PARs, expressed on macrophages, in the response to Acanthamoeba trophozoites and might provide useful insight into Acanthamoeba infections and their future treatments.
Original languageEnglish
Pages (from-to)e12612
JournalParasite Immunology
Early online date21 Dec 2018
DOIs
Publication statusE-pub ahead of print - 21 Dec 2018

Keywords

  • macrophages
  • cytokines
  • proteases
  • protease activated receptors
  • PAR1
  • PAR2

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