Treatment of Refractory Mucosal Leishmaniasis Is Associated with Parasite Overexpression of HSP70 and ATPase and Reduced Host Hydrogen Peroxide Production (Brief Report).

Autor:	Urdapilleta AAA; Post-Graduation Program in Clinical Medicine (PPGCM), Faculty of Medicine (FM), Campus Universitário Darcy Ribeiro, University of Brasília (UnB), UnB Área 1-Asa Norte, Brasilia 70910-900, DF, Brazil., Santos Alfani AO; Post-Graduation Program in Clinical Medicine (PPGCM), Faculty of Medicine (FM), Campus Universitário Darcy Ribeiro, University of Brasília (UnB), UnB Área 1-Asa Norte, Brasilia 70910-900, DF, Brazil.; Federal Institute of Brasília, Brasília 70910-900, DF, Brazil., Barroso DH; Post-Graduation Program in Clinical Medicine (PPGCM), Faculty of Medicine (FM), Campus Universitário Darcy Ribeiro, University of Brasília (UnB), UnB Área 1-Asa Norte, Brasilia 70910-900, DF, Brazil.; Dermatology Service, University Hospital of Brasília, Faculty of Medicine, University of Brasília (UnB), Brasilia 70910-900, DF, Brazil.; Dermatomycology Laboratory, School of Medicine, University of Brasília (UnB), Brasilia 70910-900, DF, Brazil., Vinecky F; Post-Graduation Program, Embrapa Cenargen, Brasilia 70910-900, DF, Brazil., Amaral Vaz Bandeira SDG; Post-Graduation Program in Clinical Medicine (PPGCM), Faculty of Medicine (FM), Campus Universitário Darcy Ribeiro, University of Brasília (UnB), UnB Área 1-Asa Norte, Brasilia 70910-900, DF, Brazil., Andrade AC; Molecular Genetics Laboratory (LGM-NTBio), Embrapa, Cenargen, Brasilia 70910-900, DF, Brazil., Taquita JA; Post-Graduation Program, Embrapa Cenargen, Brasilia 70910-900, DF, Brazil.; Molecular Genetics Laboratory (LGM-NTBio), Embrapa, Cenargen, Brasilia 70910-900, DF, Brazil.; Embrapa Recursos Genéticos e Biotecnologia, Brasilia 70910-900, DF, Brazil., Bastos IMD; Pathogen-Interaction Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília (UnB), Brasilia 70910-900, DF, Brazil., Sampaio RNR; Post-Graduation Program in Clinical Medicine (PPGCM), Faculty of Medicine (FM), Campus Universitário Darcy Ribeiro, University of Brasília (UnB), UnB Área 1-Asa Norte, Brasilia 70910-900, DF, Brazil.; Dermatology Service, University Hospital of Brasília, Faculty of Medicine, University of Brasília (UnB), Brasilia 70910-900, DF, Brazil.; Dermatomycology Laboratory, School of Medicine, University of Brasília (UnB), Brasilia 70910-900, DF, Brazil.; Post-Graduation Program in Health Sciences (PGHC), Faculty of Health Sciences, University of Brasilia (UnB), Brasilia 70910-900, DF, Brazil.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2024 Sep 30; Vol. 12 (10). Date of Electronic Publication: 2024 Sep 30.
DOI:	10.3390/biomedicines12102227
Abstrakt:	Background: Mucosal leishmaniasis (ML) is a deforming type of American Tegumentary Leishmaniasis caused by Leishmania ( Viannia ) braziliensis that frequently does not respond to treatment. Despite its relapsing clinical course, few parasites are usually found in mucosal lesions. Host and parasite factors may be responsible for this paradox in the pathogenesis of the disease, allowing for both a low parasite burden and the inability of the host to clear and eliminate the disease. Methods and Results: In this work, we present a clinical case of relapsing ML that was treated for 25 years without success with SbV, N-methyl glucamine, sodium stibogluconate, amphotericin B deoxycholate, gabromycin, antimonial plus thalidomide, liposomal amphotericin B, Leishvacin (a vaccine made in Brazil) and miltefosine. In a comparative analysis using nanoscale liquid chromatography coupled with tandem mass spectrometry of protein extracts of L. ( V. ) braziliensis promastigotes isolated from the patient and from the reference strain (MHOM/BR/94/M15176), we observed increases in ATPase and HSP70 protein levels in the parasite. We also observed an impairment in the production of hydrogen peroxide by peripheral mononuclear blood monocytes (PBMCs), as assessed by the horseradish peroxidase-dependent oxidation of phenol red. Conclusions: We hypothesise that these parasite molecules may be linked to the impairment of host parasiticidal responses, resulting in Leishmania persistence in ML patients.
Databáze:	MEDLINE
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