Parasite limiting macrophages promote IL-17 secretion in naive bovine CD4⁺ T-cells during Neospora caninum infection.

Neospora caninum infects bovine hosts giving rise to pro-inflammatory immune responses that can result in foetal death or spontaneous abortion, this appears to be mediated by the actions of IFN-γ on cell activation and migration/trafficking. Yet successful vaccination or natural immunity is also strongly correlated with IFN-γ production. We utilised in vitro infection of bovine macrophages to prime naive T-cell responses. Naive T-cells in contact with infected macrophages produce both IFN-γ and IL-17 in a pattern that is dependent on whether the priming macrophage was protected or non-protected. Our results may explain the apparent dual role of IFN-γ during infection if a second major pro-inflammatory cytokine, IL-17, is produced simultaneously.

Toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent IL-1ß secretion enhances parasite replication.

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-1ß 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.