Role of Interferon-Stimulated Gene Factor 3γ and Beta Interferon in HLA Class I Enhancement in Synovial Fibroblasts upon Infection with Chlamydia trachomatis

Chlamydia trachomatis infection can cause reactive arthritis that is associated with the persistence of chlamydial organisms in the joint. Fibroblasts of the synovial membrane represent host cells for Chlamydia during articular infection. In this study we investigated the expression of HLA class I molecules in synovial fibroblasts following infection with C. trachomatis D. The expression of HLA class I heavy chain (HLA-I) was up-regulated in infected cultures as shown by reverse transcription-PCR and immunoblotting. The increase in cell surface expression of HLA-I and β(2) microglobulin on infected fibroblasts was demonstrated by flow cytometric analysis. Suppression of enhanced production of interferon-stimulated gene factor 3γ (ISGF3γ) in infected cell cultures by antisense oligonucleotide treatment reduced the level of HLA-I. Blocking antibodies to beta interferon (IFN-β) inhibited the Chlamydia-induced enhancement of both ISGF3γ and HLA-I. These findings show that the up-regulation of HLA-I in synovial fibroblasts infected with C. trachomatis is caused by the induction of IFN-β, which in turn stimulates the synthesis of ISGF3γ, a transcription factor participating in the regulation of the HLA-I gene. The IFN-β-mediated expression of HLA-I on Chlamydia-infected cells may be a regulatory factor in the immune response in chlamydial infections.