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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number111033
JournalCell Reports
Volume40
Issue number1
DOIs
StatePublished - Jul 5 2022

Keywords

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

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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