Gene expression patterns associated with multidrug therapy in multibacillary leprosy

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 patie...

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Main Authors: Helen Ferreira, Thyago Leal-Calvo, Mayara Abud Mendes, Charlotte Avanzi, Philippe Busso, Andrej Benjak, Anna Maria Sales, Cássio Porto Ferreira, Márcia de Berrêdo-Pinho, Stewart Thomas Cole, Euzenir Nunes Sarno, Milton Ozório Moraes, Roberta Olmo Pinheiro
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2022.917282/full
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author Helen Ferreira
Thyago Leal-Calvo
Mayara Abud Mendes
Charlotte Avanzi
Philippe Busso
Andrej Benjak
Anna Maria Sales
Cássio Porto Ferreira
Márcia de Berrêdo-Pinho
Stewart Thomas Cole
Stewart Thomas Cole
Euzenir Nunes Sarno
Milton Ozório Moraes
Roberta Olmo Pinheiro
author_facet Helen Ferreira
Thyago Leal-Calvo
Mayara Abud Mendes
Charlotte Avanzi
Philippe Busso
Andrej Benjak
Anna Maria Sales
Cássio Porto Ferreira
Márcia de Berrêdo-Pinho
Stewart Thomas Cole
Stewart Thomas Cole
Euzenir Nunes Sarno
Milton Ozório Moraes
Roberta Olmo Pinheiro
author_sort Helen Ferreira
collection DOAJ
description 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.
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spelling doaj.art-322b90006fe1492baddc5a9e4e25637a2022-12-22T02:14:02ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-07-011210.3389/fcimb.2022.917282917282Gene expression patterns associated with multidrug therapy in multibacillary leprosyHelen Ferreira0Thyago Leal-Calvo1Mayara Abud Mendes2Charlotte Avanzi3Philippe Busso4Andrej Benjak5Anna Maria Sales6Cássio Porto Ferreira7Márcia de Berrêdo-Pinho8Stewart Thomas Cole9Stewart Thomas Cole10Euzenir Nunes Sarno11Milton Ozório Moraes12Roberta Olmo Pinheiro13Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilGlobal Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandGlobal Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandGlobal Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilCellular Microbiology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilGlobal Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandInstitut Pasteur, Paris, FranceLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilMultidrug 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.https://www.frontiersin.org/articles/10.3389/fcimb.2022.917282/fullmultibacillary leprosymultidrug therapylipid metabolismbacillary loadgene signature
spellingShingle Helen Ferreira
Thyago Leal-Calvo
Mayara Abud Mendes
Charlotte Avanzi
Philippe Busso
Andrej Benjak
Anna Maria Sales
Cássio Porto Ferreira
Márcia de Berrêdo-Pinho
Stewart Thomas Cole
Stewart Thomas Cole
Euzenir Nunes Sarno
Milton Ozório Moraes
Roberta Olmo Pinheiro
Gene expression patterns associated with multidrug therapy in multibacillary leprosy
Frontiers in Cellular and Infection Microbiology
multibacillary leprosy
multidrug therapy
lipid metabolism
bacillary load
gene signature
title Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_full Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_fullStr Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_full_unstemmed Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_short Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_sort gene expression patterns associated with multidrug therapy in multibacillary leprosy
topic multibacillary leprosy
multidrug therapy
lipid metabolism
bacillary load
gene signature
url https://www.frontiersin.org/articles/10.3389/fcimb.2022.917282/full
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