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.
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.
Cell Rep. 2022 Jul 5;40(1):111033. doi: 10.1016/j.celrep.2022.111033.
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.
脑细胞对体内入侵细菌的免疫反应以及致病菌逃避脑免疫监视的机制在很大程度上仍然未知。据信，小胶质细胞通过吞噬作用来消除细菌，这是基于体外数据得出的结论。在这里，我们发现大脑中的一小部分小胶质细胞吞噬引起新生儿脑膜炎的大肠杆菌（NMEC），但更多的小胶质细胞被激活以产生肿瘤坏死因子 alpha（TNFα），该因子激活星形胶质细胞分泌补体成分 3（C3），从而参与抗菌活性。为了逃避免疫系统的抗菌活性，NMEC 感知脑脊液（CSF）中低浓度的苏氨酸来下调鞭毛蛋白的表达，从而减少小胶质细胞 TNFα 和星形胶质细胞 C3 的产生。我们的发现可能有助于制定细菌性脑膜炎的治疗策略。
