The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/6/1931/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 12, June 21, 1999 1931-1938


Articles

Chlamydia Inhibits Interferon {gamma}–inducible Major Histocompatibility Complex Class II Expression by Degradation of Upstream Stimulatory Factor 1

Guangming Zhong, Tao Fan, and Li Liu

From the Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada

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.

Key Words: interferon {gamma} induction • major histocompatibility complex class II • chlamydia • upstream stimulatory factor 1 • protein degradation


Address correspondence to Guangming Zhong, Dept. of Medical Microbiology, University of Manitoba, 508-730 William Ave., Winnipeg, Manitoba, Canada R3E OW3. Phone: 204-789-3835; Fax: 204-789-3926; E-mail: gmzhong{at}cc.umanitoba.ca

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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