title: Chlamydia trachomatis disturbs epithelial tissue homeostasis in fallopian tubes via paracrine Wnt signaling.
abstract: The obligate intracellular pathogen Chlamydia trachomatis (Ctr) is a major cause of sexually transmitted disease and infertility worldwide. Ascending genital infections cause inflammation of fallopian tubes and subsequent scarring and occlusion. The cellular basis for such sequelae remains undetermined. We used confocal immunofluorescence microscopy to show that Ctr disrupts epithelial homeostasis in an ex vivo infection model of human fallopian tubes. Ctr triggered loss of polarity of inclusion harboring cells and of neighboring uninfected cells, as shown by subcellular redistribution of adhesion and polarity (occludin) markers. β-catenin (a component of the adherens junction and a Wnt signaling transducer) was recruited to the bacterial inclusion, suggesting a role for Wnt signaling in Ctr-mediated tissue damage. Comparative microarray analysis of infected epithelium in the presence of the Wnt secretion inhibitor (IWP2) demonstrated that the transcriptional response to Ctr infection was highly dependent on active Wnt secretion, moreover IWP2 reversed Ctr-induced tissue phenotypes. Notably, we observed the up-regulation of differentiation and proliferation biomarkers olfactomedin 4 and epithelial cell adhesion molecule, and also Ctr-induced proteolytic activation of epithelial cell adhesion molecule. Thus, acute Ctr infection activates the paracrine Wnt signaling pathway, leading to profound disruption of epithelial structure and function that facilitates the dissemination of damage beyond that of infected cells.
authors: Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors: Mirjana
authors: M
authors: Kessler
authors: Julia
authors: J
authors: Zielecki
authors: Oliver
authors: O
authors: Thieck
authors: Hans-Joachim
authors: HJ
authors: Mollenkopf
authors: Christina
authors: C
authors: Fotopoulou
authors: Thomas F
authors: TF
authors: Meyer
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D002690:Chlamydia Infections / Q000503:physiopathology*; D002692:Chlamydia trachomatis / Q000502:physiology*; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology; D005184:Fallopian Tube Diseases / Q000382:microbiology / Q000503:physiopathology*; D005187:Fallopian Tubes / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D019899:Paracrine Communication / Q000502:physiology*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D051176:beta Catenin