Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection

Detalhes bibliográficos
Autor(a) principal: Leal-Calvo, Thyago
Data de Publicação: 2021
Outros Autores: Martins, Bruna Leticia, Bertoluci, Daniele Ferreira, Rosa, Patricia Sammarco, Camargo, Rodrigo Mendes de, Germano, Giovanna Vale, Souza, Vania Nieto Brito de, Latini, Ana Carla Pereira, Moraes, Milton Ozório
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/51124
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
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spelling Leal-Calvo, ThyagoMartins, Bruna LeticiaBertoluci, Daniele FerreiraRosa, Patricia SammarcoCamargo, Rodrigo Mendes deGermano, Giovanna ValeSouza, Vania Nieto Brito deLatini, Ana Carla PereiraMoraes, Milton Ozório2022-02-09T19:15:55Z2022-02-09T19:15:55Z2021LEAL-CALVO, Thyago et al. Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection. Frontiers in Immunology, v. 12, Article 647832, p. 1 - 12, Apr. 2021.1664-3224https://www.arca.fiocruz.br/handle/icict/5112410.3389/fimmu.2021.647832engFrontiers MediaHanseníaseMacrófagosTerapia dirigida pelo hospedeiroTuberculoseMycobacterium lepraeMycobacterium lepraeMacrophageseQTLsHost-directed therapyLeprosyTuberculosisLarge-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil / Universidade Estadual Paulista. Faculdade de Medicina de Botucatu. Departamento de Doenças Tropicais. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil / Universidade Estadual Paulista. Faculdade de Medicina de Botucatu. Departamento de Doenç¸as Tropicais. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil / Universidade Estadual Paulista. Faculdade de Medicina de Botucatu. Departamento de Doenças Tropicais. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil / Universidade Estadual Paulista. Faculdade de Medicina de Botucatu. Departamento de Doenças Tropicais. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil / Universidade Estadual Paulista. Faculdade de Medicina de Botucatu. Departamento de Doenças Tropicais. Bauru, SP, Brasil.Instituto Lauro de Souza Lima. Divisão de Pesquisa e Ensino. Bauru, SP, Brasil / Universidade Estadual Paulista. Faculdade de Medicina de Botucatu. Departamento de Doenças Tropicais. Bauru, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Leprosy is a disease with a clinical spectrum of presentations that is also manifested in diverse histological features. At one pole, lepromatous lesions (L-pole) have phagocytic foamy macrophages heavily parasitized with freely multiplying intracellular Mycobacterium leprae. At the other pole, the presence of epithelioid giant cells and granulomatous formation in tuberculoid lesions (T-pole) lead to the control of M. leprae replication and the containment of its spread. The mechanism that triggers this polarization is unknown, but macrophages are central in this process. Over the past few years, leprosy has been studied using large scale techniques to shed light on the basic pathways that, upon infection, rewire the host cellular metabolism and gene expression. M. leprae is particularly peculiar as it invades Schwann cells in the nerves, reprogramming their gene expression leading to a stem-like cell phenotype. This modulatory behavior exerted by M. leprae is also observed in skin macrophages. Here, we used live M. leprae to infect (10:1 multiplicity of infection) monocyte-derived macrophages (MDMs) for 48 h and analyzed the whole gene expression profile using microarrays. In this model, we observe an intense upregulation of genes consistent with a cellular immune response, with enriched pathways including peptide and protein secretion, leukocyte activation, inflammation, and cellular divalent inorganic cation homeostasis. Among the most differentially expressed genes (DEGs) are CCL5/RANTES and CYP27B1, and several members of the metallothionein and metalloproteinase families. This is consistent with a proinflammatory state that would resemble macrophage rewiring toward granulomatous formation observed at the T-pole. Furthermore, a comparison with a dataset retrieved from the Gene Expression Omnibus of M. leprae-infected Schwann cells (MOI 100:1) showed that the patterns among the DEGs are highly distinct, as the Schwann cells under these conditions had a scavenging and phagocytic gene profile similar to M2-like macrophages, with enriched pathways rearrangements in the cytoskeleton, lipid and cholesterol metabolism and upregulated genes including MVK, MSMO1, and LACC1/FAMIN. In summary, macrophages may have a central role in defining the paradigmatic cellular (T-pole) vs. humoral (L-pole) responses and it is likely that the multiplicity of infection and genetic polymorphisms in key genes are gearing this polarization.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/51124/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALThyagoCalvo_MiltonMoraes_etal_IOC_2021.pdfThyagoCalvo_MiltonMoraes_etal_IOC_2021.pdfapplication/pdf1062220https://www.arca.fiocruz.br/bitstream/icict/51124/2/ThyagoCalvo_MiltonMoraes_etal_IOC_2021.pdf64f2187b68ef12733d54f6c5e59cb5ccMD52icict/511242022-02-09 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dc.title.pt_BR.fl_str_mv Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
title Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
spellingShingle Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
Leal-Calvo, Thyago
Hanseníase
Macrófagos
Terapia dirigida pelo hospedeiro
Tuberculose
Mycobacterium leprae
Mycobacterium leprae
Macrophages
eQTLs
Host-directed therapy
Leprosy
Tuberculosis
title_short Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
title_full Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
title_fullStr Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
title_full_unstemmed Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
title_sort Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection
author Leal-Calvo, Thyago
author_facet Leal-Calvo, Thyago
Martins, Bruna Leticia
Bertoluci, Daniele Ferreira
Rosa, Patricia Sammarco
Camargo, Rodrigo Mendes de
Germano, Giovanna Vale
Souza, Vania Nieto Brito de
Latini, Ana Carla Pereira
Moraes, Milton Ozório
author_role author
author2 Martins, Bruna Leticia
Bertoluci, Daniele Ferreira
Rosa, Patricia Sammarco
Camargo, Rodrigo Mendes de
Germano, Giovanna Vale
Souza, Vania Nieto Brito de
Latini, Ana Carla Pereira
Moraes, Milton Ozório
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Leal-Calvo, Thyago
Martins, Bruna Leticia
Bertoluci, Daniele Ferreira
Rosa, Patricia Sammarco
Camargo, Rodrigo Mendes de
Germano, Giovanna Vale
Souza, Vania Nieto Brito de
Latini, Ana Carla Pereira
Moraes, Milton Ozório
dc.subject.other.pt_BR.fl_str_mv Hanseníase
Macrófagos
Terapia dirigida pelo hospedeiro
Tuberculose
Mycobacterium leprae
topic Hanseníase
Macrófagos
Terapia dirigida pelo hospedeiro
Tuberculose
Mycobacterium leprae
Mycobacterium leprae
Macrophages
eQTLs
Host-directed therapy
Leprosy
Tuberculosis
dc.subject.en.pt_BR.fl_str_mv Mycobacterium leprae
Macrophages
eQTLs
Host-directed therapy
Leprosy
Tuberculosis
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2022-02-09T19:15:55Z
dc.date.available.fl_str_mv 2022-02-09T19:15:55Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv LEAL-CALVO, Thyago et al. Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection. Frontiers in Immunology, v. 12, Article 647832, p. 1 - 12, Apr. 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/51124
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2021.647832
identifier_str_mv LEAL-CALVO, Thyago et al. Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation in Mycobacterium leprae-Infected Monocyte-Derived Macrophages With Low Multiplicity of Infection. Frontiers in Immunology, v. 12, Article 647832, p. 1 - 12, Apr. 2021.
1664-3224
10.3389/fimmu.2021.647832
url https://www.arca.fiocruz.br/handle/icict/51124
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/51124/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/51124/2/ThyagoCalvo_MiltonMoraes_etal_IOC_2021.pdf
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