Toxoplasma gondii glycosylphosphatidylinositols up-regulate major histocompatibility complex (MHC) molecule expression on primary murine macrophages.
Toxoplasma gondii is an obligatory intracellular parasite able to block the IFN-gamma-induced up-regulation of major histocompatibility complex (MHC) class I and class II molecules. This facilitates parasite-mediated evasion of T-cell responses. Glycosylphosphatidylinositols (GPIs) are involved in the pathogenicity of protozoan parasites and we investigated if GPIs are responsible for inhibition of MHC expression on macrophages. In contrast to the blockade observed in cells infected with viable tachyzoites, T. gondii GPIs up-regulated MHC class I and class II molecules on the surface of both unstimulated and IFN-gamma-stimulated primary murine macrophages. This effect was correlated to the ability of GPIs to increase the antigen presentation to CD8(+) lymphocytes. T. gondii GPIs did not activate STAT1, one of the factors involved in the transcription of MHC class I and class II genes. However, the GPI-induced MHC class I up-regulation was abrogated by SN50, a specific NF-KB inhibitor. Up-regulation of surface MHC molecules by GPIs may lead to the elimination of non-infected cells of the host immune system, contributing to the immune escape strategy of T. gondii.
Debierre-Grockiego
Françoise
F
Institut für Virologie, AG Parasitologie, Philipps Universität Marburg, Marburg, Germany.
Molitor
Nicole
N
Schwarz
Ralph T
RT
Lüder
Carsten G K
CG
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000276:immunology* / Q000302:isolation & purification; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D015854:Up-Regulation
D017261:Glycosylphosphatidylinositols; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; D010047:Ovalbumin