Abstract
Following a Chlamydia trachomatis infection, the host immune response is characterized by its recognition via Toll-like and Nod-like Receptors, and the subsequent activation of interferon (IFN)-γ-mediated signaling pathways. Recently, the inflammasome-mediated host cell response has emerged to play a role in the physiopathology of C. trachomatis infection. Here we investigated, for the first time, the interaction of IFN-γ and inflammasome in an in vitro model of C. trachomatis-infected primary human synovial cells. Chlamydial replication as well as the expression of caspase-1, IL-1β, as well as IL-18 and IL-6, were assayed. Our results demonstrated the inhibitory activity of IFN-γ by interfering with the inflammasome network through the downregulation of caspase-1 mRNA expression. In addition, the ability of C. trachomatis to hinder the inflammasome pathway favoring its intracellular survival within synovial cells, was observed. Overall, our data suggest a potential mechanism of immune evasion by C. trachomatis in synovial cells, that may be contested by IFN-γ.
Highlights
Chlamydia trachomatis, an obligate intracellular pathogen, is the leading cause of bacterial sexually transmitted diseases worldwide, with more than 130 million new cases per year [1]
The main results of our study show that: (i) C. trachomatis may affect the canonical inflammasome pathway, productively infecting primary human synovial cells; (ii) IFN-γ inflammasome pathway, productively infecting primary human synovial cells; (ii) IFN-γ inhibits C. trachomatis replication by partly acting on the host-cell immune response, most inhibits C. trachomatis replication by partly acting on the host-cell immune response, most likely via the regulation of the inflammasome network
The basis for caspase-1 stimulation of chlamydial infection is not well defined [32] and remains poorly characterized in our human synovial cell model, we found that exposure of C. trachomatis-infected cells to IFN-γ may modulate the canonical inflammasome pathway by reducing the gene expression of caspase-1
Summary
An obligate intracellular pathogen, is the leading cause of bacterial sexually transmitted diseases worldwide, with more than 130 million new cases per year [1]. C. trachomatis genital infection manifests as urethritis and cervicitis in women, and urethritis in men, it is often asymptomatic, leading to chronic complications like reactive arthritis (ReA) [2,3,4]. The host cell response begins with the activation of a complex network of immune receptors and their unique downstream signaling pathways, resulting in the induction of proinflammatory cytokines involved in either the elimination of C. trachomatis or tissue damage related to chronic inflammatory state. The ability of C. trachomatis to infect synovial cells, as evidenced by the presence of chlamydial inclusions in human synovial fibroblasts [11], suggested its potential direct role in the development of ReA. Chlamydial inclusion is unique among intracellular pathogens and represents a chlamydial survival strategy since it provides a protected vacuole where
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