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Publication : An endometrial organoid model of interactions between Chlamydia and epithelial and immune cells.

First Author  Dolat L Year  2021
Journal  J Cell Sci Volume  134
Issue  5 PubMed ID  33468625
Mgi Jnum  J:380007 Mgi Id  MGI:8279105
Doi  10.1242/jcs.252403 Citation  Dolat L, et al. (2021) An endometrial organoid model of interactions between Chlamydia and epithelial and immune cells. J Cell Sci 134(5)
abstractText  Our understanding of how the obligate intracellular bacterial pathogen Chlamydia trachomatis reprograms the function of infected cells in the upper genital tract is largely based on observations made in cell culture with transformed epithelial cell lines. Here, we describe a primary organoid system derived from endometrial tissue to recapitulate epithelial cell diversity, polarity and ensuing responses to Chlamydia infection. Using high-resolution and time-lapse microscopy, we catalog the infection process in organoids from invasion to egress, including the reorganization of the cytoskeleton and positioning of intracellular organelles. We show this model is amenable to screening C. trachomatis mutants for defects in the fusion of pathogenic vacuoles, the recruitment of intracellular organelles and inhibition of cell death. Moreover, we reconstructed a primary immune cell response by co-culturing infected organoids with neutrophils, and determined that effectors like CPAF (also known as CT858) and TepP (also known as CT875) limit the recruitment of neutrophils to infected organoids. Collectively, our model can be applied to study the cell biology of Chlamydia infections in three-dimensional structures that better reflect the diversity of cell types and polarity encountered by Chlamydia in their animal hosts.
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