title: Toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent IL-1β secretion enhances parasite replication.
abstract: Alternatively activated macrophages (AAM) are a key feature Th2 immunity and have been associated with a variety of roles during helminth infection. The role this cell subset plays in protozoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rTgPrx) derived from Toxoplasma gondii on murine macrophage phenotype in vitro. RTgPrx has been previously associated with the maintainance of parasite oxidative balance. Here our experiments show that rTgPrx promotes AAM as indicated by high arginase-1 (arg-1), YM1 and FIZZ expression via both signal transducer and activator of transcription (STAT)6-dependent and -independent mechanisms. Additionally rTgPrx treatment reduced caspase-1 activity and IL-1β secretion, while simultaneously increasing IL-10 release. Furthermore the in vitro replication of T. gondii (RH strain) was enhanced when macrophages were treated with rTgPrx. This is in contrast with the previously described effects of a Plasmodium berghei ANKA 2-cys-peroxiredoxin that promotes pro-inflammatory cytokine production. These results highlight the role of T. gondii derived redox enzymes as important immune modulators and potentially indicate a role for AAM in modulating immunopathology and promoting parasite replication during T. gondii infection.
authors.affiliation: School 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.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Marshall
authors.forename: Hany M
authors.initials: HM
authors.lastname: Elshekiha
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Flynn
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D054464:Peroxiredoxins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology
chemical_list: D053583:Interleukin-1beta; D011994:Recombinant Proteins; D016753:Interleukin-10; D054464:Peroxiredoxins; D020170:Caspase 1