TY  - JOUR
A1  - Koster, Stefanie
A1  - Gurumurthy, Rajendra Kumar
A1  - Kumar, Naveen
A1  - Prakash, Pon Ganish
A1  - Dhanraj, Jayabhuvaneshwari
A1  - Bayer, Sofia
A1  - Berger, Hilmar
A1  - Kurian, Shilpa Mary
A1  - Drabkina, Marina
A1  - Mollenkopf, Hans-Joachim
A1  - Goosmann, Christian
A1  - Brinkmann, Volker
A1  - Nagel, Zachary
A1  - Mangler, Mandy
A1  - Meyer, Thomas F.
A1  - Chumduri, Cindrilla
T1  - Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming
JF  - Nature Communications
N2  - Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.
KW  - Chlamydia
KW  - HPV
KW  - cellular reprogramming
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301349
VL  - 13
IS  - 1
ER  -