Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy

Abstract Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been in...

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Main Authors: Christine Dambietz, Michael Heming, Tobias J. Brix, Andreas Schulte-Mecklenbeck, Phil-Robin Tepasse, Catharina C. Gross, Jonel Trebicka, Heinz Wiendl, Gerd Meyer zu Hörste
Format: Article
Language:English
Published: BMC 2024-07-01
Series:BMC Neurology
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Online Access:https://doi.org/10.1186/s12883-024-03742-9
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author Christine Dambietz
Michael Heming
Tobias J. Brix
Andreas Schulte-Mecklenbeck
Phil-Robin Tepasse
Catharina C. Gross
Jonel Trebicka
Heinz Wiendl
Gerd Meyer zu Hörste
author_facet Christine Dambietz
Michael Heming
Tobias J. Brix
Andreas Schulte-Mecklenbeck
Phil-Robin Tepasse
Catharina C. Gross
Jonel Trebicka
Heinz Wiendl
Gerd Meyer zu Hörste
author_sort Christine Dambietz
collection DOAJ
description Abstract Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.
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spelling doaj-art-33ec184b3ce34f3fa8e275347fc6142b2025-01-19T12:28:09ZengBMCBMC Neurology1471-23772024-07-0124111910.1186/s12883-024-03742-9Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapyChristine Dambietz0Michael Heming1Tobias J. Brix2Andreas Schulte-Mecklenbeck3Phil-Robin Tepasse4Catharina C. Gross5Jonel Trebicka6Heinz Wiendl7Gerd Meyer zu Hörste8Department of Neurology With Institute of Translational Neurology, University Hospital MünsterDepartment of Neurology With Institute of Translational Neurology, University Hospital MünsterInstitute of Medical Informatics, University of MünsterDepartment of Neurology With Institute of Translational Neurology, University Hospital MünsterDepartment of Gastroenterology, Hepatology, Endocrinology and Infectiology, University Hospital MünsterDepartment of Neurology With Institute of Translational Neurology, University Hospital MünsterDepartment of Gastroenterology, Hepatology, Endocrinology and Infectiology, University Hospital MünsterDepartment of Neurology With Institute of Translational Neurology, University Hospital MünsterDepartment of Neurology With Institute of Translational Neurology, University Hospital MünsterAbstract Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.https://doi.org/10.1186/s12883-024-03742-9Fungal meningitisCryptococcus neoformansHIVAntifungal therapyIntrathecal immunityFlow cytometry
spellingShingle Christine Dambietz
Michael Heming
Tobias J. Brix
Andreas Schulte-Mecklenbeck
Phil-Robin Tepasse
Catharina C. Gross
Jonel Trebicka
Heinz Wiendl
Gerd Meyer zu Hörste
Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
BMC Neurology
Fungal meningitis
Cryptococcus neoformans
HIV
Antifungal therapy
Intrathecal immunity
Flow cytometry
title Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
title_full Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
title_fullStr Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
title_full_unstemmed Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
title_short Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
title_sort severe csf immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
topic Fungal meningitis
Cryptococcus neoformans
HIV
Antifungal therapy
Intrathecal immunity
Flow cytometry
url https://doi.org/10.1186/s12883-024-03742-9
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