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

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

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pagese12612
JournalParasite Immunology
Early online date21 Dec 2018
DOIs
Publication statusE-pub ahead of print - 21 Dec 2018

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Acanthamoeba
Macrophage Activation
Peptide Hydrolases
Macrophages
Interleukin-12
Interleukin-6
Trophozoites
Proteinase-Activated Receptors
Infection
Protease Inhibitors
Innate Immunity
Virulence

Keywords

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

Cite this

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title = "Acanthamoeba proteases contribute to macrophage activation through PAR1, but not PAR2",
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.",
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Acanthamoeba proteases contribute to macrophage activation through PAR1, but not PAR2. / Cano, Antonella; Mattana, Antonella; Henriquez, Fiona L.; Alexander, James; Roberts, Craig W.

In: Parasite Immunology, 21.12.2018, p. e12612.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acanthamoeba proteases contribute to macrophage activation through PAR1, but not PAR2

AU - Cano, Antonella

AU - Mattana, Antonella

AU - Henriquez, Fiona L.

AU - Alexander, James

AU - Roberts, Craig W.

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/12/21

Y1 - 2018/12/21

N2 - 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.

AB - 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.

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KW - cytokines

KW - proteases

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KW - PAR2

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