Abstract
Numerous studies have shown that exosomes play a regulatory role in a variety of biological processes as well as in disease development and progression. However, exosome-mediated intercellular communication between brain microvascular endothelial cells (BMECs) and astrocytes during meningitic Escherichia coli (E. coli)–induced neuroinflammation remains largely unknown. Here, by using in vivo and in vitro models, we demonstrate that exosomes derived from meningitic E. coli–infected BMECs can activate the inflammatory response of astrocytes. A label-free quantitation approach coupled with LC-MS/MS was used to compare the exosome proteomic profiles of human BMECs (hBMECs) in response to meningitic E. coli infection. A total of 57 proteins exhibited significant differences in BMEC-derived exosomes during the infection. Among these proteins, growth differentiation factor 15 (GDF15) was significantly increased in BMEC-derived exosomes during the infection, which triggered the Erk1/2 signaling pathway and promoted the activation of astrocytes. The identification and characterization of exosome protein profiles in BMECs during meningitic E. coli infection will contribute to the understanding of the underlying pathogenic mechanisms from the perspective of intercellular communication between BMECs and astrocytes, and provide new insights for future prevention and treatment of E. coli meningitis.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request. The datasets generated and analyzed during the current study are available via the PRIDE database under identifier PXD021064.
Abbreviations
- BBB:
-
blood–brain barrier
- BMECs:
-
brain microvascular endothelial cells
- BP:
-
biological process
- CC:
-
cellular component
- CNS:
-
central nervous system
- DAPI:
-
4′,6-diamidino-2-phenylindole
- E. coli :
-
Escherichia coli
- FBS:
-
fetal bovine serum
- FITC:
-
fluorescein isothiocyanate
- GDF15:
-
growth differentiation factor 15
- GFAP:
-
glial fibrillary acidic protein
- GO:
-
Gene Ontology
- hBMECs:
-
human brain microvascular endothelial cells
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- MF:
-
molecular function
- MS:
-
mass spectrometry
- NTA:
-
nanoparticle tracking analysis
- PBS:
-
phosphate-buffered saline
- SD:
-
standard deviation
- TEM:
-
transmission electron microscopy
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Funding
This work was supported by grants from the National Key Research and Development Program of China (2021YDF1800800), the National Natural Science Foundation of China (NSFC) (32122086 and 32102749), the China Postdoctoral Science Foundation (2022M721277 and 2021T140242), the Natural Science Foundation of Hubei Province (2021CFA016), the Fundamental Research Funds for the Central Universities (2662023PY005), and the China Agriculture Research System of MOF and MARA (CARS-35).
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S.Z., R.Y., and X.Q. performed all experiments. R.Y. and S.Z. analyzed the data and drafted the manuscript. J.W. and J.F. participated in project planning and preparation of exosomes. C.T. and H.C. provided technical and administrative support. X.W. conceived of the project, coordinated and supervised the experiments, and revised the manuscript.
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All animal experiments in this study were conducted in accordance with the Guide for the Care and Use of Laboratory Animals of the China National Institutes of Health. All procedures and handling techniques were approved by the Committee for the Protection, Supervision, and Control of Experiments on Animals of Huazhong Agricultural University (Approval No. SCXK2020-0019, Animal Welfare Assurance No. 202306010004).
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Yang, R., Qu, X., Zhi, S. et al. Exosomes Derived from Meningitic Escherichia coli–Infected Brain Microvascular Endothelial Cells Facilitate Astrocyte Activation. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04044-4
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DOI: https://doi.org/10.1007/s12035-024-04044-4