1. Microbiology and Infectious Disease
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Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

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Cite this article as: eLife 2021;10:e64159 doi: 10.7554/eLife.64159

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

  1. Anahita Bakochi

    Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8144-8525
  2. Tirthankar Mohanty

    Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Paul Theodor Pyl

    Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Carlos Alberto Gueto-Tettay

    Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Lars Malmström

    Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9885-9312
  6. Adam Linder

    Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Johan Malmström

    Department of Clinical Sciences, Lund University, Lund, Sweden
    For correspondence
    johan.malmstrom@med.lu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2889-7169

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.

Reviewing Editor

  1. Benjamin F Cravatt, The Scripps Research Institute, United States

Publication history

  1. Received: October 20, 2020
  2. Accepted: April 4, 2021
  3. Accepted Manuscript published: April 6, 2021 (version 1)
  4. Version of Record published: April 13, 2021 (version 2)

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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