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Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

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...

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Autores principales: Bakochi, Anahita, Mohanty, Tirthankar, Pyl, Paul Theodor, Gueto-Tettay, Carlos Alberto, Malmström, Lars, Linder, Adam, Malmström, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043743/
https://www.ncbi.nlm.nih.gov/pubmed/33821792
http://dx.doi.org/10.7554/eLife.64159
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author Bakochi, Anahita
Mohanty, Tirthankar
Pyl, Paul Theodor
Gueto-Tettay, Carlos Alberto
Malmström, Lars
Linder, Adam
Malmström, Johan
author_facet Bakochi, Anahita
Mohanty, Tirthankar
Pyl, Paul Theodor
Gueto-Tettay, Carlos Alberto
Malmström, Lars
Linder, Adam
Malmström, Johan
author_sort Bakochi, Anahita
collection PubMed
description 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 multiprotein 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.
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spelling pubmed-80437432021-04-21 Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis Bakochi, Anahita Mohanty, Tirthankar Pyl, Paul Theodor Gueto-Tettay, Carlos Alberto Malmström, Lars Linder, Adam Malmström, Johan eLife Microbiology and Infectious Disease 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 multiprotein 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. eLife Sciences Publications, Ltd 2021-04-06 /pmc/articles/PMC8043743/ /pubmed/33821792 http://dx.doi.org/10.7554/eLife.64159 Text en © 2021, Bakochi et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Bakochi, Anahita
Mohanty, Tirthankar
Pyl, Paul Theodor
Gueto-Tettay, Carlos Alberto
Malmström, Lars
Linder, Adam
Malmström, Johan
Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
title Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
title_full Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
title_fullStr Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
title_full_unstemmed Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
title_short Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
title_sort cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043743/
https://www.ncbi.nlm.nih.gov/pubmed/33821792
http://dx.doi.org/10.7554/eLife.64159
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