The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/54564 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. |
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Rosa, Thabatta Leal Silveira AndrezoMendes, Mayara AbudLinhares, Natasha Ribeiro CardosoRodrigues, Thais FernandaDias, André AlvesLeal-Calvo, ThyagoGandini, MarianaFerreira, HelenCosta, Fabrício da Mota RamalhoSales, Ana MariaAmadeu, Thaís PortoSchmitz, VeronicaPinheiro, Roberta OlmoRodrigues, Luciana SilvaMoraes, Milton OzórioPessolani, Maria Cristina Vidal2022-08-10T14:09:16Z2022-08-10T14:09:16Z2022ROSA, Thabatta L. S. A. et al. The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum. Frontiers in Medicine, v. 9, Article 899998, p. 1 - 15, June 2022.2298-858Xhttps://www.arca.fiocruz.br/handle/icict/5456410.3389/fmed.2022.899998engFrontiers MediaImunopatogêneseReação à HanseníaseInterferons tipo ICélulas dendríticas plasmocitóidesEritema nodoso hansênicoImmunopathogenesisLeprosy reactionType I interferonsPlasmacytoid dendritic cellsErythema nodosum leprosumThe Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosuminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Laboratório de Imunopatologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.In leprosy patients, acute inflammatory episodes, known as erythema nodosum leprosum (ENL), are responsible for high morbidity and tissue damage that occur during the course of Mycobacterium leprae infection. In a previous study, we showed evidence implicating DNA-sensing via TLR9 as an important inflammatory pathway in ENL. A likely important consequence of TLR9 pathway activation is the production of type I interferons (IFN-I) by plasmacytoid dendritic cells (pDCs), also implicated in the pathogenesis of several chronic inflammatory diseases. In this study, we investigated whether the IFN-I pathway is activated during ENL. Blood samples and skin lesions from multibacillary patients diagnosed with ENL were collected and the expression of genes of the IFN-I pathway and interferon-stimulated genes were compared with samples collected from non-reactional multibacillary (NR) patients. Whole blood RNAseq analysis suggested higher activation of the IFN-I pathway in ENL patients, confirmed by RT-qPCR. Likewise, significantly higher mRNA levels of IFN-I-related genes were detected in ENL skin biopsies when compared to NR patient lesions. During thalidomide administration, the drug of choice for ENL treatment, a decrease in the mRNA and protein levels of some of these genes both in the skin and blood was observed. Indeed, in vitro assays showed that thalidomide was able to block the secretion of IFN-I by peripheral blood mononuclear cells in response to M. leprae sonicate or CpG-A, a TLR9 ligand. Finally, the decreased frequencies of peripheral pDCs in ENL patients, along with the higher TLR9 expression in ENL pDCs and the enrichment of CD123C cells in ENL skin lesions, suggest the involvement of these cells as IFN-I producers in this type of reaction. Taken together, our data point to the involvement of the pDC/type I IFN pathway in the pathogenesis of ENL, opening new avenues in identifying biomarkers for early diagnosis and new therapeutic targets for the better management of this reactional episode.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/54564/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALThabatta_Rosa_HelenFerreira_etal_IOC_2022.pdfThabatta_Rosa_HelenFerreira_etal_IOC_2022.pdfapplication/pdf2680148https://www.arca.fiocruz.br/bitstream/icict/54564/2/Thabatta_Rosa_HelenFerreira_etal_IOC_2022.pdfac9954d397237dd139ce0c214017c447MD52icict/545642022-08-10 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| dc.title.pt_BR.fl_str_mv |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| title |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| spellingShingle |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum Rosa, Thabatta Leal Silveira Andrezo Imunopatogênese Reação à Hanseníase Interferons tipo I Células dendríticas plasmocitóides Eritema nodoso hansênico Immunopathogenesis Leprosy reaction Type I interferons Plasmacytoid dendritic cells Erythema nodosum leprosum |
| title_short |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| title_full |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| title_fullStr |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| title_full_unstemmed |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| title_sort |
The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum |
| author |
Rosa, Thabatta Leal Silveira Andrezo |
| author_facet |
Rosa, Thabatta Leal Silveira Andrezo Mendes, Mayara Abud Linhares, Natasha Ribeiro Cardoso Rodrigues, Thais Fernanda Dias, André Alves Leal-Calvo, Thyago Gandini, Mariana Ferreira, Helen Costa, Fabrício da Mota Ramalho Sales, Ana Maria Amadeu, Thaís Porto Schmitz, Veronica Pinheiro, Roberta Olmo Rodrigues, Luciana Silva Moraes, Milton Ozório Pessolani, Maria Cristina Vidal |
| author_role |
author |
| author2 |
Mendes, Mayara Abud Linhares, Natasha Ribeiro Cardoso Rodrigues, Thais Fernanda Dias, André Alves Leal-Calvo, Thyago Gandini, Mariana Ferreira, Helen Costa, Fabrício da Mota Ramalho Sales, Ana Maria Amadeu, Thaís Porto Schmitz, Veronica Pinheiro, Roberta Olmo Rodrigues, Luciana Silva Moraes, Milton Ozório Pessolani, Maria Cristina Vidal |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Rosa, Thabatta Leal Silveira Andrezo Mendes, Mayara Abud Linhares, Natasha Ribeiro Cardoso Rodrigues, Thais Fernanda Dias, André Alves Leal-Calvo, Thyago Gandini, Mariana Ferreira, Helen Costa, Fabrício da Mota Ramalho Sales, Ana Maria Amadeu, Thaís Porto Schmitz, Veronica Pinheiro, Roberta Olmo Rodrigues, Luciana Silva Moraes, Milton Ozório Pessolani, Maria Cristina Vidal |
| dc.subject.other.pt_BR.fl_str_mv |
Imunopatogênese Reação à Hanseníase Interferons tipo I Células dendríticas plasmocitóides Eritema nodoso hansênico |
| topic |
Imunopatogênese Reação à Hanseníase Interferons tipo I Células dendríticas plasmocitóides Eritema nodoso hansênico Immunopathogenesis Leprosy reaction Type I interferons Plasmacytoid dendritic cells Erythema nodosum leprosum |
| dc.subject.en.pt_BR.fl_str_mv |
Immunopathogenesis Leprosy reaction Type I interferons Plasmacytoid dendritic cells Erythema nodosum leprosum |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. |
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2022 |
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2022-08-10T14:09:16Z |
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2022-08-10T14:09:16Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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ROSA, Thabatta L. S. A. et al. The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum. Frontiers in Medicine, v. 9, Article 899998, p. 1 - 15, June 2022. |
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https://www.arca.fiocruz.br/handle/icict/54564 |
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2298-858X |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fmed.2022.899998 |
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ROSA, Thabatta L. S. A. et al. The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum. Frontiers in Medicine, v. 9, Article 899998, p. 1 - 15, June 2022. 2298-858X 10.3389/fmed.2022.899998 |
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