Polybacterial intracellular coinfection of epithelial stem cells in periodontitis
Quinn T. Easter, Bruno Fernandes Matuck, Germán Beldorati Stark, Catherine L. Worth, Alexander V. Predeus, Brayon Fremin, Khoa Huynh, Vaishnavi Ranganathan, Diana Pereira, Theresa Weaver, Kathryn Miller, Paola Perez, Akira Hasuike, Zhaoxu Chen, Mandy Bush, Blake M. Warner, Janice Lee, Shannon M. Wallet, Inês Sequeira, Katarzyna M. Tyc, Jinze Liu, Kang I. Ko, Sarah A. Teichmann, Kevin M. Byrd
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.
Datasets
1. An Integrated Single Cell Meta-atlas of Human Periodontitis
Metadata
organism_ontology_term_id
tissue_ontology_term_id
suspension_type
cell_type_ontology_term_id
Annotated Cell Sets
Study
GSE
Sample ID
assay_ontology_term_id
Tooth Type
Anterior vs Posterior
Tooth #/Region
disease_ontology_term_id
sex_ontology_term_id
self_reported_ethnicity_ontology_term_id
development_stage_ontology_term_id
donor_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
NCBITaxon:9606105918 cells UBERON:0001828105918 cells Post-capillary venule VECs15819 cells Masticatory mucosal keratinocyte3770 cells Lining mucosal keratinocyte3208 cells Vascular smooth muscle cells3001 cells Conventional dendritic cells2188 cells Macrophages/Monocytes2129 cells Lymphatic endothelial cell 11661 cells Mucosal-associated invariant T cells1617 cells Gamma delta-T cells1249 cells Suprabasal keratinocytes1217 cells Sulcus/junction epithelial keratinocytes1115 cells Plasmacytoid dendritic cells605 cells Cells in the cell cycle (mixed cells)389 cells Lymphatic endothelial cell 2170 cells Langerhans cells149 cells Anterior/Posterior6809 cells Anterior Mandible3862 cells Bucal gingival margin UR3/UL32954 cells Upper 3rd molar2782 cells Buccal gingival margin UR6375 cells HANCESTRO:000554799 cells HANCESTRO:000822291 cells HsapDv:000013916473 cells HsapDv:000011512413 cells HsapDv:000009010063 cells Williams_GSE164241_GSM50050558154 cells Williams_GSE164241_GSM50050527633 cells Williams_GSE164241_GSM50050576512 cells Williams_GSE164241_GSM51770436335 cells Williams_GSE164241_GSM51770446310 cells Williams_GSE164241_GSM51770405901 cells Williams_GSE164241_GSM50050625114 cells Williams_GSE164241_GSM50050535065 cells Williams_GSE164241_GSM51770425024 cells Williams_GSE164241_GSM51770394035 cells Williams_GSE164241_GSM50050613862 cells Caetano_GSE152042_GSM46008983631 cells Williams_GSE164241_GSM50050563443 cells Caetano_GSE152042_GSM46008993103 cells Williams_GSE164241_GSM51770412975 cells Caetano_GSE152042_GSM46008972954 cells Williams_GSE164241_GSM50050492914 cells Williams_GSE164241_GSM50050582564 cells Williams_GSE164241_GSM50050482215 cells Williams_GSE164241_GSM50050541986 cells Williams_GSE164241_GSM50050501838 cells Williams_GSE164241_GSM50050591695 cells Williams_GSE164241_GSM50050511681 cells Pagella_GSE161267_GSM49041371277 cells Williams_GSE164241_GSM5005060882 cells Pagella_GSE161267_GSM4904135587 cells Pagella_GSE161267_GSM4904134477 cells Pagella_GSE161267_GSM4904136441 cells Caetano_GSE152042_GSM4600896375 cells Pagella_GSE161267_GSM4904138348 cells endothelial cell of venule15819 cells capillary endothelial cell4011 cells endothelial cell of artery3117 cells vascular associated smooth muscle cell3001 cells conventional dendritic cell2188 cells endothelial cell of lymphatic vessel1831 cells mucosal invariant T cell1617 cells gamma-delta T cell1249 cells natural killer cell1235 cells mature NK T cell1043 cells regulatory T cell1018 cells T-helper 17 cell625 cells plasmacytoid dendritic cell605 cells Hispanic or Latin American8654 cells African American4995 cells Native American1986 cells 45-year-old human stage16473 cells 21-year-old human stage12413 cells 25-44 year-old human stage10063 cells 24-year-old human stage8154 cells 57-year-old human stage7633 cells 38-year-old human stage6310 cells 35-year-old human stage5065 cells 34-year-old human stage4744 cells 22-year-old human stage4067 cells 28-year-old human stage4035 cells 39-year-old human stage3443 cells human adult stage3130 cells 32-year-old human stage2975 cells 51-year-old human stage2914 cells 44-year-old human stage2564 cells 30-year-old human stage2331 cells 31-year-old human stage2215 cells 61-year-old human stage1838 cells 42-year-old human stage1695 cells 37-year-old human stage1681 cells 26-year-old human stage1561 cells 29-year-old human stage614 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/71f4bccf-53d4-4c12-9e80-e73bfb89e398
Alias names
GSE152042, GSE161267, GSE164241
Cite this study
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. and Miller, K., 2023. Polybacterial intracellular coinfection of epithelial stem cells in periodontitis. bioRxiv, pp.2023-08. https://doi.org/10.1101/2023.08.23.554343
