Abstract
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)α, IFNβ, and IFNγ 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 IFNγ, whereas IFN-I proved to be ineffective. Furthermore, IFNγ greatly upregulated all the PRRs and ISGs examined. In conclusion, IFNγ exhibited a potent anti-Chlamydia activity in human synovial cells as well as the ability to induce a strong increase of innate immune pathways.
Highlights
Chlamydia trachomatis is an obligate intracellular bacterium with a unique developmental cycle characterized by the extracellular infectious elementary body (EB), which invades the host cell, and the intracellular replicative reticulate body (RB), responsible for the multiplication within the host [1]
We investigated the cytotoxicity of type I and II IFNs on human synovial fibroblasts via MTT assay
We evaluated the effects of IFNα, IFNβ, and IFNγ on the infection and replication phases of C. trachomatis developmental cycle in an in vitro infection model of primary human synovial fibroblasts
Summary
Chlamydia trachomatis is an obligate intracellular bacterium with a unique developmental cycle characterized by the extracellular infectious elementary body (EB), which invades the host cell, and the intracellular replicative reticulate body (RB), responsible for the multiplication within the host [1]. C. trachomatis is still an important public health problem worldwide, because of the impact of asymptomatic genital infections in both women (90%) and men (50%), favoring the onset of severe chronic complications, including reactive arthritis (ReA) in both genders [2,3,4]. It is estimated, that approximately 4–8% of patients will develop ReA one to six weeks after a urogenital C. trachomatis infection [5]. As for most bacterial infections, the host immune response, mediated by the production of a plethora of cytokines and other immune mediators, is involved in the protection against C. trachomatis infection, as well as the induction of an increased inflammatory state, contributing to tissue damage [11,12,13]
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