Toxoplasma gondii inhibits MHC class II expression in neural antigen-presenting cells by down-regulating the class II transactivator CIITA.
Major histocompatibility complex (MHC) class II expression by microglia and astrocytes is critical for CD4+-mediated immune responses within the central nervous system. Here, we demonstrate that the obligate intracellular parasite, Toxoplasma gondii, down-regulates activation-induced MHC class II expression in human-derived glioblastoma cells as well as in primary astrocytes and microglia from cortices of rat fetuses. Down-regulation of MHC class II proteins was predominantly observed in parasite-positive, but not parasite-negative, host cells of T. gondii-infected cell cultures. MHC class II transcript levels induced by IFN-gamma alone or in combination with TNF-alpha were also clearly diminished after parasitic infection. Furthermore, T. gondii dose-dependently down-regulated the transcript levels of the class II transactivator CIITA. These results suggest that T. gondii partially evade CD4+-mediated intracerebral immune responses, a mechanism which may contribute to long-term persistence of the parasite within the CNS.
Lüder
Carsten G K
CG
Department of Bacteriology, Georg-August-University of Göttingen, Kreuzbergring 57, 37075 Göttingen, Germany. clueder@gwdg.de
Lang
Christine
C
Giraldo-Velasquez
Mario
M
Algner
Michaela
M
Gerdes
Jens
J
Gross
Uwe
U
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000469:parasitology
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma