6533b7d8fe1ef96bd126974a

RESEARCH PRODUCT

Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1α

subject

description

The obligate intracellular protozoan parasite Toxoplasma gondii is able to establish persistent infections within human and animal hosts. We have shown recently that T. gondii down-regulates IFN-γ-induced MHC class II expression in murine bone marrow-derived macrophages (BMMΦ). As shown in this study, the capacity of IFN-γ-activated murine BMMΦ to present ovalbumin to CD4+ T cell hybridomas was dose-dependently inhibited by T. gondii. IFN-γ-induced up-regulation of H2-Aa, H2-Ab, H2-Eb, H2-Ma, H2-Mb, H2-Oa and invariant chain transcripts was prominently down-regulated by T. gondii. Furthermore, mRNA levels of class II transactivator and interferon-regulatory factor-1 were significantly diminished. Electromobilityshift assays demonstrated a decrease in the binding activity of nuclear extracts to the IFN-γ-activated site after infection with T. gondii, indicating parasitic interference with IFN-γ-induced signaling. However, neither the expression of the IFN-γR nor the IFN-γ-induced tyrosine phosphorylation of IFN-γR α chain and signal transducer and activator of transcription (STAT) 1α was diminished by T. gondii. IFN-γ-induced nuclear translocation of STAT1α was nevertheless inhibited after infection as demonstrated by immunofluorescence microscopy and subcellular fractionation analyses. In conclusion, this novel mechanism of microbial interference with MHC class II gene expression may contribute to intracellular survival and establishment of persistent infection with T. gondii.