Infection of human organoids supports an intestinal niche for Chlamydia trachomatis

Several reports suggest that intestinal tissue may be a natural niche for Chlamydia trachomatis infection and a reservoir for persistent infections in the human body. Due to the human specificity of the pathogen and the lack of suitable host models, there is limited knowledge on this topic. In our study, we modelled the course of the chlamydial infection in human primary gastrointestinal (GI) epithelial cells originating from patient-derived organoids. We show that GI cells are resistant to apical infection and C. trachomatis needs access to the basolateral membrane to establish an infection. Transmission electron microscopy analysis reveals the presence of both normal as well as aberrant chlamydial developmental forms in the infected cells, suggesting a possible cell-type specific nature of the infection. Furthermore, we show that the plasmid-encoded Pgp3 is an important virulence factor for the infection of human GI cells. This is the first report of C. trachomatis infection in human primary intestinal epithelial cells supporting a possible niche for chlamydial infection in the human intestinal tissue. Author summaryChlamydial infection has a high global prevalence and is a major health concern. Untreated infections may cause complications and lead to serious health problems, especially in women. Although the infection is usually localized to the genital tract, experiments performed in a mouse infection model as well as the accumulating clinical data suggest that the human gastrointestinal (GI) tract might represent a hidden infection niche and a source of reinfections. In our study, we used the advantages of the organoid technology to model the chlamydial infection in patient-derived primary GI epithelial cells. We were able to show that these cells are resistant to the infection, however, Chlamydia could utilize a basolateral entry route for efficient infection. Chlamydia form either normal or persistent-like developmental forms in these GI epithelial cells. We also showed the importance of the plasmid-mediated virulence in the infection of human GI cells. The results obtained in the GI infection model replicated phenotypes predicted and expected for Chlamydia human intestinal infection, and therefore support a role of the human GI tract as a potential niche for chlamydial infection.