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Articles |
–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)-
–inducible major histocompatibility complex (MHC) class II expression. However, the IFN-
–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-
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-
induction of class II transactivator (CIITA) but not of IRF-1 and ICAM-1. CIITA is an obligate mediator of IFN-
–inducible MHC class II expression. Thus, diminished CIITA expression as a result of USF-1 degradation may account for the suppression of the IFN-
–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.
Key Words: interferon
induction major histocompatibility complex class II chlamydia upstream stimulatory factor 1 protein degradation
Abbreviations used: CIITA, class II transactivator; IDO, indoleamine 2,3-dioxygenase; IRF, interferon regulatory factor; JAK, Janus tyrosine kinase; MOI, multiplicity of infection; MOMP, major outer membrane protein; RT, reverse transcriptase; STAT, signal transducers and activators of transcription; USF, upstream stimulatory factor.
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