Variation of Hypoxia Inducible Factor 1 alpha subunit (HIF-1α) and Prolyl Hydroxylase Domain 2 (PHD2) transcripts in Toxoplasma gondii infection: a preliminary comparative analysis.

Toxoplasma gondii infects nearly one-third of the world population [1]. Virtually all species can be infected, but the parasite spreads more easily among some species (e.g. Pig) that infect humans more often than others (e.g. Horse). Investigating which host pathways are modulated by T. gondii and if there is an interspecies variation is interesting both for human and animal medicine. Experiments performed in cultured cells have shown that T. gondii activates the host HIF-1 to persist inside the cell. This activation is not due to an increased synthesis of HIF-1α coding mRNA, but to the stabilization of the protein subunit, via down regulation of PHD2 abundance and/or activity [2]. Since those data came from the analysis of experimentally infected cells, the aim of this study was to confirm results in naturally infected animals and compare species which differ in susceptibility to Toxoplasmosis. T. gondii target tissues (brain stem and diaphragm) were collected post mortem from pigs and horses. Infected or uninfected condition was assessed by immunoenzymatic assay. HIF-1α and PHD2 mRNA synthesis was measured by Real-time PCR. Results were processed byΔΔCt method and expressed as fold change among the target mRNAs, normalized to β-actin. Performed analysis revealed that T. gondii doesn’t significantly alter neither HIF-1α nor PHD2 transcripts levels. Comparing uninfected animals from a naturally resistant species (Horse) and a naturally susceptible one (Pig), a significantly higher level of HIF-1α transcripts was unexpectedly detected in brain stem of the first one compared to the latter, while no difference was observed for PHD2. Further analysis should be performed to assess if this variation of brain HIF-1α transcripts in Horse compared to Pig influences the protein abundance. References 1. Pereira-Chioccola VL et al. Future Microbiology (2009) 4, 1363-1379. 2. Wiley M et al. Journal of Biological Chemistry (2010) 285, 26976-26986