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bioRxiv · 10.1101/2024.12.02.626423

Insights into Intestinal Barrier Disruption During Long-Term Gut Chlamydia Colonization in Mice: A Single-Cell Transcriptomic Approach

Tian, Q.·Jiang, Y.·Xie, S.·Shu, C.·Wan, J.·Huang, Y.·Wang, L.·Zhang, Q.·Zhou, Z.·Sun, X.·Zhang, T.
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Abstract

Chlamydia trachomatis, an intracellular pathogen, stands as the most prevalent sexually transmitted bacterial infection among women globally. Traditionally recognized as a genital pathogen, recent research indicates that the gastrointestinal tract may also act as a reservoir for its long-term colonization. However, the mechanisms underlying Chlamydias ability to persist in the gut remain poorly understood. This gap in knowledge limits our ability to develop effective treatments for persistent Chlamydia infections. In this study we utilized single-cell RNA sequencing to analyze the gene expression profiles and cellular heterogeneity of mouse colonic tissues during Chlamydia long-term infection. This approach provided detailed insights into the transcriptional changes and cellular interactions involved in the persistence of Chlamydia in the gut. Our results revealed significant alterations in the gene expression profiles of various intestinal cell populations, with distinct molecular pathways contributing to Chlamydia persistence. Notably, we observed a reduction in the expression of markers associated with epithelial tight junctions, indicating a potential breakdown of the intestinal epithelial barrier. This impairment may facilitate the penetration of Chlamydia into deeper tissues and contribute to the initiation of infection. We also found dysregulation of the transcriptional networks in goblet cells and an imbalance in communication between immune and epithelial cells. These disruptions were linked to the pathogens ability to establish persistent colonization and infection. IMPORTANCEFew studies have explored Chlamydia persistence in the gastrointestinal tract. In this study, we use single-cell RNA sequencing to identify the molecular and cellular mechanisms driving the pathogens long-term colonization. Our findings provide crucial insights into how Chlamydia overcomes the hosts immune defenses and epithelial barriers to establish chronic infection in the gut. Notably, we identify disruption of epithelial tight junctions and an imbalance in immune-cell interactions, offering new avenues for therapeutic interventions aimed at restoring mucosal integrity and preventing persistent infection.

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Tian, Q., Jiang, Y., Xie, S., Shu, C., Wan, J., Huang, Y., Wang, L., Zhang, Q., Zhou, Z., Sun, X., Zhang, T.. 2024-12-02. Insights into Intestinal Barrier Disruption During Long-Term Gut Chlamydia Colonization in Mice: A Single-Cell Transcriptomic Approach. https://doi.org/10.1101/2024.12.02.626423

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