Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , |
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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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 |
format |
article |
status_str |
publishedVersion |
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 |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
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reponame:Repositório Digital do Instituto Evandro Chagas (Patuá) instname:Instituto Evandro Chagas (IEC) instacron:IEC |
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Instituto Evandro Chagas (IEC) |
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IEC |
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IEC |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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