Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis

Detalhes bibliográficos
Autor(a) principal: Christensen, Stephen M
Data de Publicação: 2019
Outros Autores: Belew, Ashton T, El-Sayed, Najib M, Tafuri, Wagner L, Silveira, Fernando Tobias, Mosser, David M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/3618
Resumo: Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.
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spelling Christensen, Stephen MBelew, Ashton TEl-Sayed, Najib MTafuri, Wagner LSilveira, Fernando TobiasMosser, David M2019-03-28T17:12:42Z2019-03-28T17:12:42Z2019CHRISTENSEN, Stephen M. et al. Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis. PLoS Neglected Tropical Diseases, v. 13, n. 3, e0007152, p. 1-23, Mar. 2019.1935-2727https://patua.iec.gov.br/handle/iec/361810.1371/journal.pntd.0007152Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.University of Maryland. Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute. College Park, United States of America.University of Maryland. Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute. College Park, United States of America / University of Maryland. Center for Bioinformatics and Computational Biology. College Park, United States of America.University of Maryland. Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute. College Park, United States of America / University of Maryland. Center for Bioinformatics and Computational Biology. College Park, United States of America.Universidade Federal de Minas Geras. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / University of Pará. Tropical Medicine Nucleus. Belém, PA, Brazil.University of Maryland. Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute. College Park, United States of America.engPublic Library of ScienceHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLeishmaniose Tegumentar Difusa / parasitologiaLeishmaniose / parasitologiaExpressão GênicaParasitos / parasitologiaInterações Hospedeiro-Parasitainfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.pdfHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.pdfapplication/pdf3990875https://patua.iec.gov.br/bitstreams/344bbd63-ad61-4fef-9f9f-4ccf2c7a387d/downloadefaa1bae0b7d115006fe847be4059469MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/f0ceae9b-0221-4bc3-bfd1-aa27ae8b6694/download11832eea31b16df8613079d742d61793MD52TEXTHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.pdf.txtHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.pdf.txtExtracted texttext/plain92401https://patua.iec.gov.br/bitstreams/457b9104-1e3e-47df-9271-4dad5c3c5438/downloadfa9318135b8af0a9df5f7b92a55b5921MD55THUMBNAILHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.pdf.jpgHost and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.pdf.jpgGenerated Thumbnailimage/jpeg5843https://patua.iec.gov.br/bitstreams/aab7f0db-4863-4aec-b339-ad2743610ded/download7f585e7baae27fb41ac05d90b7dad8e1MD56iec/36182022-10-20 21:08:36.341oai:patua.iec.gov.br:iec/3618https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T21:08:36Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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
dc.title.pt_BR.fl_str_mv Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
title Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
spellingShingle Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
Christensen, Stephen M
Leishmaniose Tegumentar Difusa / parasitologia
Leishmaniose / parasitologia
Expressão Gênica
Parasitos / parasitologia
Interações Hospedeiro-Parasita
title_short Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
title_full Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
title_fullStr Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
title_full_unstemmed Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
title_sort Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
author Christensen, Stephen M
author_facet Christensen, Stephen M
Belew, Ashton T
El-Sayed, Najib M
Tafuri, Wagner L
Silveira, Fernando Tobias
Mosser, David M
author_role author
author2 Belew, Ashton T
El-Sayed, Najib M
Tafuri, Wagner L
Silveira, Fernando Tobias
Mosser, David M
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Christensen, Stephen M
Belew, Ashton T
El-Sayed, Najib M
Tafuri, Wagner L
Silveira, Fernando Tobias
Mosser, David M
dc.subject.decsPrimary.pt_BR.fl_str_mv Leishmaniose Tegumentar Difusa / parasitologia
Leishmaniose / parasitologia
Expressão Gênica
Parasitos / parasitologia
Interações Hospedeiro-Parasita
topic Leishmaniose Tegumentar Difusa / parasitologia
Leishmaniose / parasitologia
Expressão Gênica
Parasitos / parasitologia
Interações Hospedeiro-Parasita
description Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-03-28T17:12:42Z
dc.date.available.fl_str_mv 2019-03-28T17:12:42Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.citation.fl_str_mv CHRISTENSEN, Stephen M. et al. Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis. PLoS Neglected Tropical Diseases, v. 13, n. 3, e0007152, p. 1-23, Mar. 2019.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/3618
dc.identifier.issn.-.fl_str_mv 1935-2727
dc.identifier.doi.-.fl_str_mv 10.1371/journal.pntd.0007152
identifier_str_mv CHRISTENSEN, Stephen M. et al. Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis. PLoS Neglected Tropical Diseases, v. 13, n. 3, e0007152, p. 1-23, Mar. 2019.
1935-2727
10.1371/journal.pntd.0007152
url https://patua.iec.gov.br/handle/iec/3618
dc.language.iso.fl_str_mv eng
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