Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation

Mirjana Kessler, Karen Hoffmann, Kristin Fritsche, Volker Brinkmann, Hans-Joachim Mollenkopf, Oliver Thieck, Ana Rita Teixeira da Costa, Elena I. Braicu, Jalid Sehouli, Mandy Mangler, Hilmar Berger and Thomas F. Meyer ()
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Mirjana Kessler: Max Planck Institute for Infection Biology
Karen Hoffmann: Max Planck Institute for Infection Biology
Kristin Fritsche: Max Planck Institute for Infection Biology
Volker Brinkmann: Max Planck Institute for Infection Biology
Hans-Joachim Mollenkopf: Max Planck Institute for Infection Biology
Oliver Thieck: Max Planck Institute for Infection Biology
Ana Rita Teixeira da Costa: Max Planck Institute for Infection Biology
Elena I. Braicu: Charité University Medicine
Jalid Sehouli: Charité University Medicine
Mandy Mangler: Auguste-Viktoria-Klinikum
Hilmar Berger: Max Planck Institute for Infection Biology
Thomas F. Meyer: Max Planck Institute for Infection Biology

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Chronic infections of the fallopian tubes with Chlamydia trachomatis (Ctr) cause scarring and can lead to infertility. Here we use human fallopian tube organoids and genital Ctr serovars D, K and E for long-term in vitro analysis. The epithelial monolayer responds with active expulsion of the bacteria into the lumen and with compensatory cellular proliferation—demonstrating a role of epithelial homeostasis in the defense against this pathogen. In addition, Ctr infection activates LIF signaling, which we find to be an essential regulator of stemness in the organoids. Infected organoids exhibit a less differentiated phenotype with higher stemness potential, as confirmed by increased organoid forming efficiency. Moreover, Ctr increases hypermethylation of DNA, which is an indicator of accelerated molecular aging. Thus, the chronic organoid infection model suggests that Ctr has a long-term impact on the epithelium. These heritable changes might be a contributing factor in the development of tubal pathologies, including the initiation of high grade serous ovarian cancer.

Date: 2019
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DOI: 10.1038/s41467-019-09144-7

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