Infection of human organoids supports an intestinal niche for Chlamydia trachomatis

PLoS Pathog. 2024 Aug 22;20(8):e1012144. doi: 10.1371/journal.ppat.1012144. eCollection 2024 Aug.

Abstract

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.

MeSH terms

  • Antigens, Bacterial / metabolism
  • Bacterial Proteins
  • Chlamydia Infections* / microbiology
  • Chlamydia trachomatis* / physiology
  • Epithelial Cells / microbiology
  • Humans
  • Intestinal Mucosa / microbiology
  • Organoids* / microbiology
  • Organoids* / pathology

Substances

  • pgp3 protein, Chlamydia
  • Antigens, Bacterial
  • Bacterial Proteins

Grants and funding

This work was funded by the Deutsche Forschungsgemeinschaft (DFG) in the RTG 2157/2 3D Infect and the SFB 1583 DECIDE to S.B., T.R. and the European Research Council (grant no. ERC-2018-ADG/NCI-CAD) to T.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.