Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis

• Published in: Cell reports (Cambridge) Vol. 33; no. 9; p. 108438
• Main Authors: Golomb, Samantha M., Guldner, Ian H., Zhao, Anqi, Wang, Qingfei, Palakurthi, Bhavana, Aleksandrovic, Emilija A., Lopez, Jacqueline A., Lee, Shaun W., Yang, Kai, Zhang, Siyuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020; Elsevier
• Subjects: aging; Animals; brain; Brain - immunology; brain immunity; CITE-seq; CNS; dysbiosis; Dysbiosis - immunology; Gastrointestinal Microbiome - immunology; gut microbiota; Humans; Immunity, Innate - immunology; Single-Cell Analysis - methods; single-cell sequencing; single-cell sequencing; brain immunity; CITE-seq; CNS; aging; brain; gut microbiota; dysbiosis
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108438

Phenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C+ monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (Tscm) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases. [Display omitted] •CNS native immune cells exhibit age-associated inflammatory qualities•Ly6C+ monocytes display transcriptional plasticity in the aged mouse brain•Innate lymphoid cell plasticity reflects age-associated chronic neuroinflammation•Gut dysbiosis affects innate lymphoid cell plasticity only in aged mice Golomb et al. perform cellular indexing of transcriptomes and epitopes by sequencing on immune cells from the brains of young and aged female mice with and without antibiotics-induced gut dysbiosis. Single-cell analyses reveal transcriptional plasticity of canonically identified monocytes and innate lymphoid cells in the aged brain.