Expression of interferon regulatory factors and indoleamine 2,3-dioxygenase in Chlamydia trachomatis-infected synovial fibroblasts

Synovial fibroblasts probably represent host cells for Chlamydia trachomati s during initial intra-articular infection in reactive arthritis. In vitro synovial cells produce interferon-beta (IFN-beta) in response to chlamydial infection. IFN-beta expression can be activated by interferon regulatory f actor-1 (IRF-1) and interferon-stimulated gene factor 3 gamma(ISGF3 gamma). In this study, we demonstrate that infection of synovial fibroblasts with C. trachomatis serotype D induced the expression of IRF-1 mRNA as shown by reverse transcription-PCR. Tumor necrosis factor-alpha (TNF-alpha) stimulat ion enhanced IRF-1 mRNA levels in infected cells and was required to detect IRF-1 protein by immunoblotting. The level of constitutively expressed IRF -2 was not significantly affected after infection. C. trachomatis was found to cause an up-regulation of ISGF3 gamma protein in synovial cells. Induct ion of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is an important mechanism of the host cell response to control intracellul ar infection by chlamydiae. It has been described that IRF-1 can induce IDO gene expression. Infection of synovial fibroblasts alone in the absence of exogenous cytokine induced the expression of IDO mRNA which was enhanced b y TNF-alpha treatment. The stimulation of IRF-1, ISGF3 gamma, and IDO expre ssion was most effective when viable chlamydiae were used as inoculum. Neut ralization of IFN-beta in the culture medium of infected cells diminished b ut did not abrogate expression of IRF-1, ISGF3 gamma, and IDO. The increase d production of IRF-1 and ISGF3 gamma in C. trachomatis-infected synovial f ibroblasts may contribute to induction of IFN-beta and IDO.