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Toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent IL-1β secretion enhances

Edward S Marshall1, Hany M Elshekiha, Mohamed-Ali Hakimi

  • 1School of Veterinary Medicine & Science, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, UK. robin.flynn@nottingham.ac.uk.

Veterinary Research
|June 29, 2011
PubMed

Insights

Toxoplasma gondii redox enzyme (rTgPrx) promotes alternatively activated macrophages (AAM), reducing inflammation and enhancing parasite replication. This study explores rTgPrx

Area of Science:

  • Immunology
  • Parasitology
  • Cell Biology

Background:

  • Alternatively activated macrophages (AAM) are crucial in Th2 immunity and helminth infections.
  • The role of AAM in protozoan infections, like Toxoplasma gondii, is largely unknown.
  • Toxoplasma gondii possesses redox enzymes, such as rTgPrx, involved in parasite oxidative balance.

Purpose of the Study:

  • To investigate the effects of the Toxoplasma gondii redox enzyme (rTgPrx) on murine macrophage phenotype in vitro.
  • To determine if rTgPrx influences macrophage polarization towards an alternatively activated state.
  • To assess the impact of rTgPrx on inflammatory cytokine production and parasite replication.

Main Methods:

  • Treatment of murine macrophages with purified rTgPrx.
  • Analysis of macrophage phenotype markers, including arginase-1 (arg-1), YM1, and FIZZ expression.
  • Assessment of STAT6-dependent and -independent signaling pathways.
  • Measurement of caspase-1 activity, IL-1β, and IL-10 secretion.
  • Quantification of in vitro Toxoplasma gondii (RH strain) replication.

Main Results:

  • rTgPrx treatment induced AAM phenotype, evidenced by increased arginase-1, YM1, and FIZZ expression.
  • AAM induction occurred through both signal transducer and activator of transcription (STAT)6-dependent and -independent pathways.
  • rTgPrx reduced caspase-1 activity and IL-1β secretion, while increasing IL-10 release.
  • In vitro replication of Toxoplasma gondii was enhanced in rTgPrx-treated macrophages.
  • These findings contrast with the pro-inflammatory effects of Plasmodium berghei ANKA 2-cys-peroxiredoxin.

Conclusions:

  • Toxoplasma gondii redox enzymes, like rTgPrx, act as significant immune modulators.
  • rTgPrx promotes an alternatively activated macrophage phenotype.
  • AAM may play a role in modulating immunopathology and facilitating parasite replication during Toxoplasma gondii infection.

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