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.
Hao Sun  1 ,  Xuehua Wan  2 ,  Yu Fan  2 ,  Peng Liu  2 ,  Yajun Song  1 ,  Ningyu Zhu  3 ,  Zhifeng Duan  1 ,  Qian Wang  2 ,  Fang Chen  2 ,  Changhong Zhou  2 ,  Yangyang Zheng  1 ,  Peng Ding  2 ,  Fenxia Liu  2 ,  Lu Feng  1 ,  Kwang Sik Kim  3 ,  Lei Wang  4
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: [email protected].
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.
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