Your browser doesn't support javascript.
loading
Pathogenic bacteria exploit transferrin receptor transcytosis to penetrate the blood-brain barrier.
Cheng, Zhihui; Zheng, Yangyang; Yang, Wen; Sun, Hongmin; Zhou, Fangyu; Huang, Chuangjie; Zhang, Shuwen; Song, Yingying; Liang, Qi'an; Yang, Nan; Li, Meifang; Liu, Bin; Feng, Lu; Wang, Lei.
Afiliação
  • Cheng Z; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Zheng Y; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
  • Yang W; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Sun H; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
  • Zhou F; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Huang C; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
  • Zhang S; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Song Y; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
  • Liang Q; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Yang N; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
  • Li M; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Liu B; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
  • Feng L; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • Wang L; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China.
Proc Natl Acad Sci U S A ; 120(39): e2307899120, 2023 09 26.
Article em En | MEDLINE | ID: mdl-37733740
The human blood-brain barrier (BBB) comprises a single layer of brain microvascular endothelial cells (HBMECs) protecting the brain from bloodborne pathogens. Meningitis is among the most serious diseases, but the mechanisms by which major meningitis-causing bacterial pathogens cross the BBB to reach the brain remain poorly understood. We found that Streptococcus pneumoniae, group B Streptococcus, and neonatal meningitis Escherichia coli commonly exploit a unique vesicle fusion mechanism to hitchhike on transferrin receptor (TfR) transcytosis to cross the BBB and illustrated the details of this process in human BBB model in vitro and mouse model. Toll-like receptor signals emanating from bacteria-containing vesicles (BCVs) trigger K33-linked polyubiquitination at Lys168 and Lys181 of the innate immune regulator TRAF3 and then activate the formation of a protein complex containing the guanine nucleotide exchange factor RCC2, the small GTPase RalA and exocyst subcomplex I (SC I) on BCVs. The distinct function of SEC6 in SC I, interacting directly with RalA on BCVs and the SNARE protein SNAP23 on TfR vesicles, tethers these two vesicles and initiates the fusion. Our results reveal that innate immunity triggers a unique modification of TRAF3 and the formation of the HBMEC-specific protein complex on BCVs to authenticate the precise recognition and selection of TfR vesicles to fuse with and facilitate bacterial penetration of the BBB.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Células Endoteliais Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Células Endoteliais Idioma: En Ano de publicação: 2023 Tipo de documento: Article