Single-cell analysis reveals changes in BCG vaccine-injected mice modeling tuberculous meningitis brain infection

Xiaolin Zhang; Zhangyan Zhao; Qingguo Wu; Lei Wang; Liqun Li; Mei Wang; Yang Ren; Lei Pan; Haicheng Tang; Feng Li

doi:10.1016/j.celrep.2023.112177

Single-cell analysis reveals changes in BCG vaccine-injected mice modeling tuberculous meningitis brain infection

Cell Rep. 2023 Mar 28;42(3):112177. doi: 10.1016/j.celrep.2023.112177. Epub 2023 Mar 1.

Authors

Xiaolin Zhang¹, Zhangyan Zhao¹, Qingguo Wu¹, Lei Wang¹, Liqun Li¹, Mei Wang¹, Yang Ren¹, Lei Pan¹, Haicheng Tang², Feng Li³

Affiliations

¹ Department of Respiratory Disease and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
² Department of Respiratory Disease and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China. Electronic address: tanghaicheng@shphc.org.cn.
³ Department of Respiratory Disease and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China. Electronic address: lifeng@shphc.org.cn.

PMID: 36862557
DOI: 10.1016/j.celrep.2023.112177

Abstract

Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications are observed in up to 50% of patients affected. Here, attenuated Mycobacterium bovis are injected into the cerebellum of mice, and histopathological images and cultured colonies confirm successful brain infection. Then, whole-brain tissue is dissected for 10X Genomics single-cell sequencing, and we acquire 15 cell types. Transcriptional changes of inflammation processes are found in multiple cell types. Specifically, Stat1 and IRF1 are shown to mediate inflammation in macrophages and microglia. For neurons, decreased oxidative phosphorylation activity in neurons is observed, which corresponds to TBM clinical symptoms of neurodegeneration. Finally, ependymal cells present prominent transcriptional changes, and decreased FERM domain containing 4A (Frmd4a) may contribute to TBM clinical symptoms of hydrocephalus and neurodegeneration. This study shows a single-cell transcriptome of M. bovis infection in mice and improves the understanding of brain infection and neurological complications in TBM.

Keywords: CP: Neuroscience; Frmd4a; immune response; metabolism; neurological complications; single-cell sequencing; tuberculous meningitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
BCG Vaccine / adverse effects
Brain
Inflammation / complications
Mice
Mycobacterium tuberculosis*
Single-Cell Analysis
Tuberculosis, Meningeal* / complications
Tuberculosis, Meningeal* / diagnosis
Tuberculosis, Meningeal* / microbiology

Substances

BCG Vaccine