One example for host cell modulation by T. gondii is the CP127374 protein ROP16, a member of the ROP2 family. Secretion of ROP16 activates STAT3 and STAT6 and reduces proinflammatory cytokines [39]. However, the accumulation of Irg6 at the PV of an avirulent parasite was not altered regardless of the presence of a virulent PV in the same host cell. We therefore conclude that the accumulation of the IRGs is a PV-autonomous feature determined by the virulence of the containing parasite. Since the virulence factors ROP18 and ROP5 are discussed to be responsible for IRG blocking [19, 40], one possible mechanism could be the local targeting of the PV of these two ROP proteins to prevent the IRG accumulation of virulent T. gondii strains. Further experiments have to delineate the different compositions of virulent and avirulent PVs.
5. ConclusionIn conclusion, we have shown that in astrocytes avirulent and virulent T. gondii strains significantly differ in recruitment of the analyzed IRGs to their individual PVs. The amount of IRG recruitment correlates with the inhibitory properties of the astrocyte suggesting a role for this process in parasite virulence. In the accumulation process at the PV, Irga6 and Irgb6 reveal different kinetics and an altered localisation profile. Furthermore, the virulence of the parasite in terms of IRG recruitment seems to be determined by the individual PV of the contained tachyzoites and is not a result of the host-cell manipulation. Conflict of InterestsThe authors declare that they have no conflict of interests.Authors’ ContributionFelix P.
Lubitz performed the experiments, participated in the analysis of the data and the statistical analysis, and helped to draft the paper. Daniel Degrandi performed the experiments and analysed data. Klaus Pfeffer has revised the paper and was involved in study design. Anne K. Mausberg designed and performed the research, analyzed the data, and wrote the paper. All authors read and approved the final paper.AcknowledgmentsThe authors thank Dr. Gaby Reichmann for reagents and helpful discussion. They are highly grateful for the kind gift of Irga6 antibody to Jonathan C. Howard. Part of this study was supported by the DFG (Graduiertenkolleg 320 to Anne K. Mausberg and FOR 729 to Klaus Pfeffer). AbbreviationsIFN: Interferon IRG: Immunity-related GTPase MOI: Multiplicity of infection pi: Post infectionPV: Parasitophorous vacuoleT.
gondii:Toxoplasma Batimastat gondii.
Corticosteroid-induced osteonecrosis of the femoral head (ONFH) is a serious complication of systemic corticosteroid administration for treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), nephrotic syndrome, and rheumatoid arthritis. The prevalence of ONFH in patients receiving corticosteroids has been reported as 0.3~13% [1, 2].