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

Samantha M Golomb; Ian H Guldner; Anqi Zhao; Qingfei Wang; Bhavana Palakurthi; Emilija A Aleksandrovic; Jacqueline A Lopez; Shaun W Lee; Kai Yang; Siyuan Zhang

doi:10.1016/j.celrep.2020.108438

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

Cell Rep. 2020 Dec 1;33(9):108438. doi: 10.1016/j.celrep.2020.108438.

Authors

Affiliations

¹ Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, 1234 N. Notre Dame Avenue, South Bend, IN 46617, USA.
² Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Genomics, Disease Ecology & Global Health, University of Notre Dame, Notre Dame, IN 46656, USA.
³ Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA.
⁴ Indiana University School of Medicine, Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA.
⁵ Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN 46556, USA; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, 1234 N. Notre Dame Avenue, South Bend, IN 46617, USA; Indiana University School of Medicine, Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA. Electronic address: szhang8@nd.edu.

Abstract

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 (T_scm) 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.

Keywords: CITE-seq; CNS; aging; brain; brain immunity; dysbiosis; gut microbiota; single-cell sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / immunology*
Dysbiosis / immunology*
Gastrointestinal Microbiome / immunology*
Humans
Immunity, Innate / immunology*
Single-Cell Analysis / methods*

Abstract

Publication types

MeSH terms

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