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Polybacterial intracellular coinfection of epithelial stem cells in periodontitis

Easter, Q. T.; Matuck, B. F.; Stark, G. B.; Worth, C. L.; Predeus, A. V.; Fremin, B.; Huynh, K. T.; Ranganathan, V.; Pereira, D.; Weaver, T.; Miller, K.; Perez, P.; Hasuike, A.; Chen, Z.; Bush, M.; Qu, X.; Warner, B. M.; Lee, J.; Wallet, S. M.; Sequeira, I.; Tyc, K. M.; Liu, J.; Ko, K. I.; Teichmann, S. A.; Byrd, K. M.

2023-08-24 cell biology
10.1101/2023.08.23.554343 bioRxiv
Show abstract

Periodontitis affects billions of people worldwide. To address interkingdom relationships of microbes and niche on periodontitis, we generated the first sin-gle-cell meta-atlas of human periodontium (34-sample, 105918-cell), harmo-nizing 32 annotations across 4 studies1-4. Highly multiplexed immunofluores-cence (32-antibody; 113910-cell) revealed spatial innate and adaptive immune foci segregation around tooth-adjacent epithelial cells. Sulcular and junctional keratinocytes (SK/JKs) within epithelia skewed toward proinflammatory phe-notypes; diseased JK stem/progenitors displayed altered differentiation states and chemotactic cytokines for innate immune cells. Single-cell metagenomics utilizing unmapped reads revealed 37 bacterial species. 16S and rRNA probes detected polybacterial intracellular pathogenesis ("co-infection") of 4 species within single cells for the first time in vivo. Challenging coinfected primary human SK/JKs with lipopolysaccharide revealed solitary and synergistic ef-fects. Coinfected single-cell analysis independently displayed proinflammatory phenotypes in situ. Here, we demonstrate the first evidence of polybacterial intracellular pathogenesis in human tissues and cells--potentially influencing chronic diseases at distant sites.

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