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

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Abstract

Paracoccidioidomycosis (PCM), a systemic mycosis caused by the fungus Paracoccidioides spp. is the most prevalent fungal infection among immunocompetent patients in Latin America. The estimated frequency of central nervous system (CNS) involvement among the human immunodeficiency virus (HIV)/PCM-positive population is 2.5%. We aimed to address the impact of neuroparacoccidioidomycosis (NPCM) and HIV/NPCM co-infection on the tight junctions (TJ) and adherens junction (AJ) proteins of the CNS. Four CNS formalin-fixed paraffin-embedded (FFPE) tissue specimens were studied: NPCM, NPCM/HIV co-infection, HIV-positive without opportunistic CNS infection, and normal brain autopsy (negative control). Immunohistochemistry was used to analyze the endothelial cells and astrocytes expressions of TJ markers: claudins (CLDN)-1, -3, -5 and occludin; AJ markers: β-catenin and E-cadherin; and pericyte marker: alpha-smooth muscle actin. FFPE CNS tissue specimens were analyzed using the immunoperoxidase assay. CLDN-5 expression in the capillaries of the HIV/NPCM coinfected tissues (mixed clinical form of PCM) was lower than that in the capillaries of the HIV or NPCM monoinfected (chronic clinical form of PCM) tissues. A marked decrease in CLDN-5 expression and a compensatory increase in CLDN-1 expression in the NPCM/HIV co-infection tissue samples was observed. The authors suggest that Paracoccidioides spp. crosses the blood–brain barrier through paracellular pathway, owing to the alteration in the CLDN expression, or inside the macrophages (Trojan horse).

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Authors and Affiliations

  1. Medical Pathology Department, School of Medicine, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    Sérgio Monteiro de Almeida, Amanda Kulik & Lucia de Noronha

  2. Neuroinfection Outclinic, Hospital de Clinicas, Universidade Federal do Paraná, Rua Padre Camargo 280, Curitiba, Paraná, 80060-240, Brazil

    Sérgio Monteiro de Almeida

  3. Micology Laboratory, Hospital de Clinicas, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    Marisol Dominguez Muro

  4. Laboratório de Patologia Experimental, Escola de Medicina- Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil

    Mineia Alessandra Scaranello Malaquias, Seigo Nagashima, Caroline Busatta Vaz de Paula & Lucia de Noronha

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Contributions

SMdA: conceived and designed the study, performed research, analyzed data, contributed new methods or models, wrote the paper. AK: performed research. MM: performed research. SN: performed research. CdP: performed research. MM: conceived the study. LdN: conceived and designed the study, performed research, analyzed data, contributed new methods or models, wrote the paper.

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Correspondence to Sérgio Monteiro de Almeida.

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de Almeida, S.M., Kulik, A., Malaquias, M.A.S. et al. The Impact of Paracoccidioides spp Infection on Central Nervous System Cell Junctional Complexes. Mycopathologia 187, 567–577 (2022). https://doi.org/10.1007/s11046-022-00653-6

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