The Impact of Paracoccidioides spp Infection on Central Nervous System Cell Junctional Complexes

Sérgio Monteiro de Almeida1,2, Amanda Kulik3, Mineia Alessandra Scaranello Malaquias4

  • 1Medical Pathology Department, School of Medicine, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.

Mycopathologia
|August 3, 2022
PubMed

Insights

Neuroparacoccidioidomycosis (NPCM) with HIV co-infection alters blood-brain barrier proteins. Claudin-5 decreased, while Claudin-1 increased, suggesting fungal entry via paracellular routes or macrophages.

Area of Science:

  • Neuroscience
  • Mycology
  • Immunology

Background:

  • Paracoccidioidomycosis (PCM) is a prevalent fungal infection in Latin America.
  • Central nervous system (CNS) involvement occurs in 2.5% of HIV-positive individuals with PCM.
  • Understanding the impact of neuroparacoccidioidomycosis (NPCM) and HIV co-infection on CNS barriers is crucial.

Purpose of the Study:

  • To investigate the effects of NPCM and HIV/NPCM co-infection on tight junction (TJ) and adherens junction (AJ) proteins in the CNS.
  • To analyze the expression of specific TJ, AJ, and pericyte markers in affected CNS tissues.

Main Methods:

  • Analysis of four formalin-fixed paraffin-embedded (FFPE) CNS tissue specimens: NPCM, NPCM/HIV co-infection, HIV-positive, and normal autopsy.
  • Immunohistochemistry and immunoperoxidase assay to evaluate endothelial and astrocyte expression of CLDNs, occludin, β-catenin, E-cadherin, and alpha-smooth muscle actin.
  • Comparison of protein expression patterns across different clinical conditions.

Main Results:

  • Reduced Claudin-5 (CLDN-5) expression in capillaries of HIV/NPCM co-infected tissues compared to NPCM or HIV monoinfected tissues.
  • Significant decrease in CLDN-5 and compensatory increase in Claudin-1 (CLDN-1) expression observed in NPCM/HIV co-infection samples.
  • Alterations in TJ protein expression suggest potential disruption of the blood-brain barrier.

Conclusions:

  • Paracoccidioides spp. may breach the blood-brain barrier via paracellular pathways due to altered Claudin expression.
  • Fungal dissemination into the CNS could also occur through infected macrophages (Trojan horse mechanism).
  • These findings highlight the impact of fungal infections and HIV co-infection on CNS barrier integrity.

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