The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum

dc.creatorRosa, Thabatta Leal Silveira Andrezo
dc.creatorMendes, Mayara Abud
dc.creatorLinhares, Natasha Ribeiro Cardoso
dc.creatorRodrigues, Thais Fernanda
dc.creatorDias, André Alves
dc.creatorLeal-Calvo, Thyago
dc.creatorGandini, Mariana
dc.creatorFerreira, Helen
dc.creatorCosta, Fabrício da Mota Ramalho
dc.creatorSales, Ana Maria
dc.creatorAmadeu, Thaís Porto
dc.creatorSchmitz, Veronica
dc.creatorPinheiro, Roberta Olmo
dc.creatorRodrigues, Luciana Silva
dc.creatorMoraes, Milton Ozório
dc.creatorPessolani, Maria Cristina Vidal
dc.date2022-08-10T14:09:16Z
dc.date2022-08-10T14:09:16Z
dc.date2022
dc.date.accessioned2023-09-26T23:09:51Z
dc.date.available2023-09-26T23:09:51Z
dc.identifierROSA, 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.
dc.identifier2298-858X
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/54564
dc.identifier10.3389/fmed.2022.899998
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8887553
dc.descriptionIn 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectImunopatogênese
dc.subjectReação à Hanseníase
dc.subjectInterferons tipo I
dc.subjectCélulas dendríticas plasmocitóides
dc.subjectEritema nodoso hansênico
dc.subjectImmunopathogenesis
dc.subjectLeprosy reaction
dc.subjectType I interferons
dc.subjectPlasmacytoid dendritic cells
dc.subjectErythema nodosum leprosum
dc.titleThe Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum
dc.typeArticle


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