TY - JOUR TI - Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis AU - Bakochi, Anahita AU - Mohanty, Tirthankar AU - Pyl, Paul Theodor AU - Gueto-Tettay, Carlos Alberto AU - Malmström, Lars AU - Linder, Adam AU - Malmström, Johan A2 - Cravatt, Benjamin F A2 - Kana, Bavesh D A2 - Beck, Martin VL - 10 PY - 2021 DA - 2021/04/06 SP - e64159 C1 - eLife 2021;10:e64159 DO - 10.7554/eLife.64159 UR - https://doi.org/10.7554/eLife.64159 AB - 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. KW - proteomics KW - meningitis KW - cerebrospinal fluid JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -