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Nat Commun. 2019 Mar 18;10(1):1194. doi: 10.1038/s41467-019-09144-7.

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

Author information

1
Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
2
Department of Gynecology, Charité University Medicine, Campus Virchow, Augustenburger Platz 1, 13353, Berlin, Germany.
3
Department of Gynecology and Obstetrics, Auguste-Viktoria-Klinikum, Rubensstr. 125, 12157, Berlin, Germany.
4
Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany. meyer@mpiib-berlin.mpg.de.

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.

PMID:
30886143
PMCID:
PMC6423033
DOI:
10.1038/s41467-019-09144-7
[Indexed for MEDLINE]
Free PMC Article

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