Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
- Lund University, Sweden
Abstract
Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD023174.
Article and author information
Author details
Funding
Knut och Alice Wallenbergs Stiftelse (2017.0271)
- Johan Malmström
Vetenskapsrådet (2015-02481)
- Johan Malmström
Vetenskapsrådet (2018-05795)
- Johan Malmström
Vetenskapsrådet (2018-05973)
- Johan Malmström
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The medical ethics committees (Institutional Review Boards) of the Lund University approved of the study (decision number 790/2005 and 2016/672), and all samples were taken with the informed consent of the participants or next of kin.
Copyright
© 2021, Bakochi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
eLife 10:e64159.
https://doi.org/10.7554/eLife.64159
