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Published on: November 16, 2016
Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia Trachomatis Infection Model of
Marisa Di Pietro1, Simone Filardo1, Federica Frasca2
1Section of Microbiology, Department of Public Health and Infectious Diseases, Sapienza University, Rome 00185, Italy.
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.
Insights
Interferon-gamma (IFNγ) effectively inhibits Chlamydia trachomatis infection and replication in human synovial cells. This study shows IFNγ boosts innate immune pathways, unlike type I interferons (IFN-I).
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Chlamydia trachomatis is a common bacterial STD causing chronic issues like reactive arthritis.
- Mechanisms of Chlamydia-induced innate immune responses in synovial fibroblasts are poorly understood.
Purpose of the Study:
- Investigate the effects of interferons (IFNα, IFNβ, IFNγ) on C. trachomatis infection and replication.
- Examine the induction of pattern recognition receptors (PRRs) and IFN-related pathways by Chlamydiae.
Main Methods:
- An in vitro model using primary human synovial cells infected with C. trachomatis.
- Treatment with IFNα, IFNβ, or IFNγ before or after infection.
- Quantification of chlamydial load and expression of PRRs (TLR2, TLR3, TLR4) and IFN-stimulated genes (cGAS, STING, IRF9, ISG56, GBP1).
Main Results:
- IFNγ significantly inhibited C. trachomatis infection and replication in synovial cells.
- Type I interferons (IFN-I) were ineffective against C. trachomatis.
- IFNγ markedly upregulated PRRs and IFN-stimulated genes.
Conclusions:
- IFNγ demonstrates potent anti-Chlamydia activity in human synovial cells.
- IFNγ enhances innate immune pathway activation, suggesting a therapeutic role.
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