Bacteria reduce flagellin synthesis to evade microglia-astrocyte-driven immunity in the brain

Hao Sun; Xuehua Wan; Yu Fan; Peng Liu; Yajun Song; Ningyu Zhu; Zhifeng Duan; Qian Wang; Fang Chen; Changhong Zhou; Yangyang Zheng; Peng Ding; Fenxia Liu; Lu Feng; Kwang Sik Kim; Lei Wang

doi:10.1016/j.celrep.2022.111033

Bacteria reduce flagellin synthesis to evade microglia-astrocyte-driven immunity in the brain

Cell Rep. 2022 Jul 5;40(1):111033. doi: 10.1016/j.celrep.2022.111033.

Authors

Hao Sun¹, Xuehua Wan², Yu Fan², Peng Liu², Yajun Song¹, Ningyu Zhu³, Zhifeng Duan¹, Qian Wang², Fang Chen², Changhong Zhou², Yangyang Zheng¹, Peng Ding², Fenxia Liu², Lu Feng¹, Kwang Sik Kim³, Lei Wang⁴

Affiliations

¹ TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China; Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China; College of Life Sciences, Nankai University, Tianjin 300071, China.
² TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China; Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
³ Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁴ TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China; Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China; College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: wanglei@nankai.edu.cn.

PMID: 35793624
DOI: 10.1016/j.celrep.2022.111033

Abstract

The immune response of brain cells to invading bacteria in vivo and the mechanism used by pathogenic bacteria to escape brain immune surveillance remain largely unknown. It is believed that microglia eliminate bacteria by phagocytosis based on in vitro data. Here we find that a small percentage of microglia in the brain engulf neonatal meningitis-causing Escherichia coli (NMEC), but more microglia are activated to produce tumor necrosis factor alpha (TNFα), which activates astrocytes to secrete complement component 3 (C3) involved in anti-bacterial activity. To evade anti-bacterial activity of the immune system, NMEC senses low concentration of threonine in cerebrospinal fluid (CSF) to down-modulate the expression of flagellin and reduce microglial TNFα and astrocyte C3 production. Our findings may help develop strategies for bacterial meningitis treatment.

Keywords: CP: Immunology; astrocyte; complement; flagellin; microglia; neonatal meningitis-causing E. coli.

Publication types

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

MeSH terms

Astrocytes* / metabolism
Bacteria / metabolism
Brain / metabolism
Flagellin / metabolism
Flagellin / pharmacology
Humans
Infant, Newborn
Microglia* / metabolism
Tumor Necrosis Factor-alpha / metabolism

Substances

Tumor Necrosis Factor-alpha
Flagellin