Chlamydia inhibits interferon gamma-inducible major histocompatibility complex class II expression by degradation of upstream stimulatory factor 1.
We report that chlamydiae, which are obligate intracellular bacterial pathogens, can inhibit interferon (IFN)-gamma-inducible major histocompatibility complex (MHC) class II expression. However, the IFN-gamma-induced IFN regulatory factor-1 (IRF-1) and intercellular adhesion molecule 1 (ICAM-1) expression is not affected, suggesting that chlamydia may selectively target the IFN-gamma signaling pathways required for MHC class II expression. Chlamydial inhibition of MHC class II expression is correlated with degradation of upstream stimulatory factor (USF)-1, a constitutively and ubiquitously expressed transcription factor required for IFN-gamma induction of class II transactivator (CIITA) but not of IRF-1 and ICAM-1. CIITA is an obligate mediator of IFN-gamma-inducible MHC class II expression. Thus, diminished CIITA expression as a result of USF-1 degradation may account for the suppression of the IFN-gamma-inducible MHC class II in chlamydia-infected cells. These results reveal a novel immune evasion strategy used by the intracellular bacterial pathogen chlamydia that improves our understanding of the molecular basis of pathogenesis.
Zhong
G
G
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada. gmzhong@cc.umanitoba.ca
Fan
T
T
Liu
L
L
D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma