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Infection and Immunity, December 2006, p. 6877-6884, Vol. 74, No. 12
0019-9567/06/$08.00+0     doi:10.1128/IAI.00505-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Up-Regulation of Gamma Interferon Receptor Expression Due to Chlamydia-Toll-Like Receptor Interaction Does Not Enhance Signal Transducer and Activator of Transcription 1 Signaling

Department of Microbiology, Miami University, Oxford, Ohio

Received 28 March 2006/ Returned for modification 2 June 2006/ Accepted 28 September 2006

Gamma interferon (IFN-)-induced indoleamine dioxygenase (IDO), which inhibits chlamydial replication by reducing the availability of tryptophan, is up-regulated by interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-). The mechanisms by which this occurs include an increase in the synthesis of interferon regulatory factor-1 as well as a nuclear factor-B (NF-B)-dependent increase in the expression of IFN- receptors (IFN-R). Although Chlamydia is susceptible to IDO, it up-regulates IFN-R expression to a greater degree than either IL-1ß or TNF-, perhaps through interaction with Toll-like receptors (TLR). The purpose of this study was to determine the mechanism by which Chlamydia psittaci up-regulates IFN-R expression and evaluate this effect on IDO induction. Infection of HEK 293 cells with C. psittaci increased IFN-R expression only in cells expressing either TLR2 or TLR4 and the adaptor protein MD-2. In addition, up-regulation of IFN-R expression in Chlamydia-infected HeLa cells could be blocked either by neutralizing TLRs with anti-TLR2 and/or anti-TLR4 or by inhibiting NF-B transactivation with a proteasome inhibitor. Although the newly expressed IFN-R in Chlamydia-infected cells were capable of binding IFN-, they did not enhance IFN--induced IDO activity in a manner similar to those observed for IL-1ß and TNF-. Instead, IDO activation in Chlamydia-infected cells was no different than that induced in uninfected cells, despite the increase in IFN-R expression. Furthermore, the amount of IFN--induced signal transducer and activator of transcription 1 (STAT-1) activation in infected cells paralleled that observed in uninfected cells, suggesting that STAT-1 activation by these newly expressed receptors was impaired.

Published ahead of print on 9 October 2006.

Editor: J. L. Flynn