Chlamydia inhibits interferon γ-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.