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

Abstract

Synovial fibroblasts probably represent host cells for Chlamydia trachomatis during initial intra-articular infection in reactive arthritis. In vitro synovial cells produce interferon-β (IFN-β) in response to chlamydial infection. IFN-β expression can be activated by interferon regulatory factor-1 (IRF-1) and interferon-stimulated gene factor 3γ (ISGF3γ). 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-α (TNF-α) stimulation 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 ISGF3γ protein in synovial cells. Induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is an important mechanism of the host cell response to control intracellular 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 by TNF-α treatment. The stimulation of IRF-1, ISGF3γ, and IDO expression was most effective when viable chlamydiae were used as inoculum. Neutralization of IFN-β in the culture medium of infected cells diminished but did not abrogate expression of IRF-1, ISGF3γ, and IDO. The increased production of IRF-1 and ISGF3γ in C. trachomatis-infected synovial fibroblasts may contribute to induction of IFN-β and IDO.