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Gene expression patterns associated with multidrug therapy in multibacillary leprosy

Ferreira, Helen ; Leal-Calvo, Thyago ; Mendes, Mayara Abud ; Avanzi, Charlotte ; Busso, Philippe ; Benjak, Andrej ; Sales, Anna Maria ; Ferreira, Cássio Porto ; de Berrêdo-Pinho, Márcia ; Cole, Stewart Thomas ; Sarno, Euzenir Nunes ; Moraes, Milton Ozório ; Pinheiro, Roberta Olmo

Frontiers in cellular and infection microbiology, 2022-07, Vol.12, p.917282-917282 [Periódico revisado por pares]

Frontiers Media S.A

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  • Título:
    Gene expression patterns associated with multidrug therapy in multibacillary leprosy
  • Autor: Ferreira, Helen ; Leal-Calvo, Thyago ; Mendes, Mayara Abud ; Avanzi, Charlotte ; Busso, Philippe ; Benjak, Andrej ; Sales, Anna Maria ; Ferreira, Cássio Porto ; de Berrêdo-Pinho, Márcia ; Cole, Stewart Thomas ; Sarno, Euzenir Nunes ; Moraes, Milton Ozório ; Pinheiro, Roberta Olmo
  • Assuntos: bacillary load ; Cellular and Infection Microbiology ; gene signature ; lipid metabolism ; multibacillary leprosy ; multidrug therapy
  • É parte de: Frontiers in cellular and infection microbiology, 2022-07, Vol.12, p.917282-917282
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    This article was submitted to Clinical Microbiology, a section of the journal Frontiers in Cellular and Infection Microbiology
    Present addresses: Charlotte Avanzi, Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO, United States; Andrej Benjak, Department for BioMedical Research, Oncogenomics Laboratory, University of Bern, Bern, Switzerland
    These authors have contributed equally to this work
    Edited by: Keshar Kunja Mohanty, National JALMA Institute for Leprosy & Other Mycobacterial Diseases (ICMR), India
    Reviewed by: Vinay Kumar Pathak, The Leprosy Mission Trust India, India; Hendra Gunawan, Universitas Padjadjaran, Indonesia; Sundeep Chaitanya Vedithi, University of Cambridge, United Kingdom
  • Descrição: Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against  M. leprae . Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders ( APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6 , and IFNG ). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7 , and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1 , that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.
  • Editor: Frontiers Media S.A
  • Idioma: Inglês
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