Intrathecal production and secretion of vascular endothelial growth factor during Cryptococcal Meningitis

Frank E J Coenjaerts1, Michiel van der Flier, Pauline N M Mwinzi

  • 1Department of Acute Medicine and Infectious Diseases and Eijkman-Winkler Institute for Microbiology, University Medical Center Utrecht, The Netherlands. f.e.j.coenjaerts@lab.azu.nl.

Abstract

Insights

Vascular Endothelial Growth Factor (VEGF) is elevated in patients with cryptococcal meningitis (CM), suggesting it plays a key role in the disease. This study identifies immune cells producing VEGF in response to cryptococcal antigens.

Area of Science:

  • Neuroscience
  • Immunology
  • Infectious Diseases

Background:

  • Cryptococcal meningitis (CM) frequently causes elevated intracranial pressure (ICP) and blood-brain barrier (BBB) disruption.
  • Elevated ICP is a major factor contributing to mortality in CM patients.
  • Vascular Endothelial Growth Factor (VEGF) is implicated as a potential mediator of BBB disruption in CM.

Purpose of the Study:

  • To investigate the role of VEGF in the pathophysiology of CM.
  • To measure VEGF levels in patients with CM and healthy controls.
  • To identify the cellular sources and triggers of VEGF secretion in vitro.

Main Methods:

  • Measured VEGF levels in serum, plasma, and cerebrospinal fluid (CSF) from 95 CM patients and 63 controls.
  • Analyzed in vitro VEGF secretion induced by Cryptococcus neoformans antigens.
  • Utilized major histocompatibility complex class II antibody to investigate VEGF production pathways.

Main Results:

  • Cryptococcal antigens dose-dependently induced VEGF secretion from neutrophils, monocytes, and PBMCs.
  • VEGF production by PBMCs was significantly higher than by monocytes.
  • Patients with CM exhibited significantly elevated VEGF levels in CSF, plasma, and serum compared to controls, indicating intrathecal production.

Conclusions:

  • VEGF is implicated in the pathophysiology of cryptococcal meningitis.
  • VEGF is produced intrathecally in response to cryptococcal antigens.
  • CD4(+) T lymphocytes, stimulated by monocytes, are proposed as the primary producers of VEGF in CM.

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