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

• Published in: Mycopathologia (1975) 2022-12, Vol.187 (5-6), p.567-577
• Main Authors: de Almeida, Sérgio Monteiro, Kulik, Amanda, Malaquias, Mineia Alessandra Scaranello, Nagashima, Seigo, de Paula, Caroline Busatta Vaz, Muro, Marisol Dominguez, de Noronha, Lucia
• Format: Article
• Language: English
• Subjects: Actin; Analysis; Astrocytes; Autopsy; Biomedical and Life Sciences; Blood vessels; Blood-brain barrier; Capillaries; Central nervous system; E-cadherin; Endothelial cells; Eukaryotic Microbiology; Formaldehyde; Health aspects; HIV; HIV patients; Human immunodeficiency virus; Immunohistochemistry; Infection; Infections; Life Sciences; Macrophages; Medical Microbiology; Medical research; Medicine, Experimental; Microbial Ecology; Microbiology; Muscle proteins; Mycoses; Mycosis; Nervous system; Original Article; Paracoccidioides; Paraffin; Plant Sciences; Smooth muscle; South American blastomycosis; Spyware; Tight junctions; β-Catenin
• ISSN: 0301-486X; 1573-0832
• DOI: 10.1007/s11046-022-00653-6

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).