Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia trachomatis Infection Model of Primary Human Synovial Fibroblasts
2020
Marisa Di Pietro | Simone Filardo | Federica Frasca | Carolina Scagnolari | Martina Manera | Vincenzo Sessa | Guido Antonelli | Rosa Sessa
Chlamydia trachomatis, an obligate intracellular pathogen, is the most common cause of bacterial sexually transmitted diseases, and it is potentially responsible for severe chronic sequelae, such as reactive arthritis. To date, details of the mechanisms by which Chlamydiae induce innate antimicrobial pathways in synovial fibroblasts, are not well characterized: therefore, herein, we investigated the effects of interferon (IFN)&alpha:, IFN&beta:, and IFN&gamma: on the infection, and replication phases of the C. trachomatis developmental cycle, as well as on the induction of pattern recognition receptors (PRRs) and IFN-related pathways. To do so, we set up an in vitro chlamydial-infection model of primary human synovial cells treated with IFNs before or after the infection. We then determined the number of chlamydial inclusion forming units and inclusion size, as well as the expression of toll like receptor (TLR)2, TLR3, TLR4, cyclic GMP-AMP synthase (cGAS), stimulator of IFN gene (STING), IRF9, ISG56, and GBP1. The main result of our study is the significant inhibition of C. trachomatis infection and replication in human synovial cells following the treatment with IFN&gamma:, whereas IFN-I proved to be ineffective. Furthermore, IFN&gamma: greatly upregulated all the PRRs and ISGs examined. In conclusion, IFN&gamma: exhibited a potent anti-Chlamydia activity in human synovial cells as well as the ability to induce a strong increase of innate immune pathways.
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