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

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Christine Dambietz1, Michael Heming1, Tobias J Brix2

  • 1Department of Neurology With Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, Bldg A1 48149, Münster, Germany.

BMC Neurology
|July 3, 2024
PubMed

Insights

Cryptococcal meningitis (CM) involves fungal invasion of the central nervous system (CNS). Studies show elevated natural killer cells in HIV-negative CM patients, indicating early immune activation and disrupted barriers in HIV-positive patients.

Area of Science:

  • Immunology
  • Neuroscience
  • Infectious Diseases

Background:

  • Cryptococcal meningitis (CM) is a severe CNS fungal infection primarily affecting immunocompromised individuals.
  • Previous research on host responses in cerebrospinal fluid (CSF) is limited, with few comprehensive studies on cellular changes in CM patients.
  • Understanding cellular dynamics in the CNS is crucial for managing this life-threatening condition.

Purpose of the Study:

  • To investigate and compare cellular changes in the CSF and blood of patients with CM.
  • To differentiate immune responses in HIV-positive versus HIV-negative CM patients and compare them to controls.
  • To analyze the longitudinal changes in CSF cellularity during antifungal therapy.

Main Methods:

  • Retrospective analysis of CSF and blood samples from CM patients (n=7), HIV-positive patients without meningitis (n=13), and HIV-negative healthy controls (n=7).
  • Flow cytometry was used to analyze cellular populations in CSF and blood.
  • Comparison of cellular data between CM patients with HIV (n=3) and other immunocompromised conditions (n=4).

Main Results:

  • Elevated natural killer (NK) cells and natural killer T (NKT) cells were observed in the CSF and blood of HIV-negative CM patients, suggesting innate immune activation.
  • HIV-positive CM patients demonstrated more significant disruption of the blood-CSF barrier.
  • Follow-up CSF analysis up to 150 days revealed heterogeneous cellular recovery patterns in CM patients, with slow normalization post-treatment.

Conclusions:

  • Innate immune activation, characterized by increased NK and NKT cells, is evident in HIV-negative CM patients.
  • Blood-CSF barrier integrity is compromised in HIV-positive CM patients.
  • Cellular recovery in the CSF of CM patients is variable and often slow, even after initiating antifungal therapy.
Keywords:
Antifungal therapyCryptococcus neoformansFlow cytometryFungal meningitisHIVIntrathecal immunity

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