Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/47719 |
Resumo: | National Institutes of Health (NIH) R01-AI-149456 (https://grants.nih.gov/grants/funding/r01.htm) |
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Amorim, Camila FariasNovais, Fernanda O.Nguyen, Ba T.Nascimento, Mauricio T.Lago, JamileLago, Alexsandro S.Carvalho, Lucas PedreiraBeiting, Daniel P.Scott, Phillip2021-06-16T16:46:47Z2021-06-16T16:46:47Z2021AMORIM, Camila Farias et al. Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. PLoS Neglected Tropical Diseases, p. 1-19, 1 Apr. 2021.1935-2727https://www.arca.fiocruz.br/handle/icict/4771910.1371/journal.pntd.00093211935-2735National Institutes of Health (NIH) R01-AI-149456 (https://grants.nih.gov/grants/funding/r01.htm)National Institute of Allergy and Infectious Diseases AI 136032 (https://www.niaid.nih.gov).University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, United States of America.University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, United States of America.University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, United States of America.Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, United States of America.University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, United States of America.Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-γ within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-γ which triggers their ability to kill the intracellular parasites. Consistent with this, transcriptional analysis of patient lesions identified an interferon stimulated gene (ISG) signature. To determine whether localized L. braziliensis infection triggers a systemic immune response that may influence the disease, we performed RNA sequencing (RNAseq) on the blood of L. braziliensis-infected patients and healthy controls. Functional enrichment analysis identified an ISG signature as the dominant transcriptional response in the blood of patients. This ISG signature was associated with an increase in monocyte- and macrophage-specific marker genes in the blood and elevated serum levels IFN-γ. A cytotoxicity signature, which is a dominant feature in the lesions, was also observed in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis–another localized infection–but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests a mechanism to limit systemic spread of the parasite, as well as enhance parasite control by pre-activating cells prior to lesion entry.engPublic Library of ScienceSangueLesõesMaláriaTuberculoseExpressão genéticaLeishmanioseInterferonsCélulas exterminadoras naturaisBloodLesionsMalariaTuberculosisGene expressionLeishmaniasisInterferonsNK cellsLocalized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signatureinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/47719/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALAmorim, Camila Farias Localized....pdfAmorim, Camila Farias Localized....pdfapplication/pdf1853821https://www.arca.fiocruz.br/bitstream/icict/47719/2/Amorim%2c%20Camila%20Farias%20Localized....pdf6e1b8b7db45756397358f2c982db7c44MD52TEXTAmorim, Camila Farias Localized....pdf.txtAmorim, Camila Farias Localized....pdf.txtExtracted texttext/plain70881https://www.arca.fiocruz.br/bitstream/icict/47719/3/Amorim%2c%20Camila%20Farias%20Localized....pdf.txt3678eda9567987454fd9bf4d7587c2a6MD53icict/477192023-03-15 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| dc.title.en.fl_str_mv |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| title |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| spellingShingle |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature Amorim, Camila Farias Sangue Lesões Malária Tuberculose Expressão genética Leishmaniose Interferons Células exterminadoras naturais Blood Lesions Malaria Tuberculosis Gene expression Leishmaniasis Interferons NK cells |
| title_short |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| title_full |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| title_fullStr |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| title_full_unstemmed |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| title_sort |
Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature |
| author |
Amorim, Camila Farias |
| author_facet |
Amorim, Camila Farias Novais, Fernanda O. Nguyen, Ba T. Nascimento, Mauricio T. Lago, Jamile Lago, Alexsandro S. Carvalho, Lucas Pedreira Beiting, Daniel P. Scott, Phillip |
| author_role |
author |
| author2 |
Novais, Fernanda O. Nguyen, Ba T. Nascimento, Mauricio T. Lago, Jamile Lago, Alexsandro S. Carvalho, Lucas Pedreira Beiting, Daniel P. Scott, Phillip |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Amorim, Camila Farias Novais, Fernanda O. Nguyen, Ba T. Nascimento, Mauricio T. Lago, Jamile Lago, Alexsandro S. Carvalho, Lucas Pedreira Beiting, Daniel P. Scott, Phillip |
| dc.subject.other.pt_BR.fl_str_mv |
Sangue Lesões Malária Tuberculose Expressão genética Leishmaniose Interferons Células exterminadoras naturais |
| topic |
Sangue Lesões Malária Tuberculose Expressão genética Leishmaniose Interferons Células exterminadoras naturais Blood Lesions Malaria Tuberculosis Gene expression Leishmaniasis Interferons NK cells |
| dc.subject.en.en.fl_str_mv |
Blood Lesions Malaria Tuberculosis Gene expression Leishmaniasis Interferons NK cells |
| description |
National Institutes of Health (NIH) R01-AI-149456 (https://grants.nih.gov/grants/funding/r01.htm) |
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2021 |
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2021-06-16T16:46:47Z |
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2021-06-16T16:46:47Z |
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2021 |
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AMORIM, Camila Farias et al. Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. PLoS Neglected Tropical Diseases, p. 1-19, 1 Apr. 2021. |
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https://www.arca.fiocruz.br/handle/icict/47719 |
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1935-2727 |
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10.1371/journal.pntd.0009321 |
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1935-2735 |
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AMORIM, Camila Farias et al. Localized skin inflammation during cutaneous leishmaniasis drives a chronic, systemic IFN-γ signature. PLoS Neglected Tropical Diseases, p. 1-19, 1 Apr. 2021. 1935-2727 10.1371/journal.pntd.0009321 1935-2735 |
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