Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/252574 |
Resumo: | Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease. |
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Pietrobon, Anna JuliaAndrejew, RobertaCustódio, Ricardo Wesley AlbercaOliveira, Luana de MendonçaScholl, Juliete NathaliTeixeira, Franciane Mouradian EmidioBrito, Cyro Alves deGlaser, TalitaKazmierski, JuliaGoffinet, ChristineTurdo, Anna ClaudiaYendo, TatianaAoki, ValériaFigueiró, FabrícioBattastini, Ana Maria OliveiraUlrich, HenningBenard, GillDuarte, Alberto Jose da SilvaSato, Maria Notomi2022-12-09T04:58:49Z20221664-3224http://hdl.handle.net/10183/252574001155287Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.application/pdfengFrontiers in immunology. Lausanne. Vol. 13 (2022), 1012027, 12 p.COVID-19Trifosfato de adenosinaPurinérgicosAdenosina5'-nucleotidaseAdenosineATPCD39CD73COVID-19SARS-CoV-2Purinergic signalingDysfunctional purinergic signaling correlates with disease severity in COVID-19 patientsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001155287.pdf.txt001155287.pdf.txtExtracted Texttext/plain58098http://www.lume.ufrgs.br/bitstream/10183/252574/2/001155287.pdf.txt0b3e11eb2cd3cd61d2edef7f1a828680MD52ORIGINAL001155287.pdfTexto completo (inglês)application/pdf3412939http://www.lume.ufrgs.br/bitstream/10183/252574/1/001155287.pdfaa3ff478c53f1a4036acb30bd9e3851eMD5110183/2525742022-12-10 06:06:33.595076oai:www.lume.ufrgs.br:10183/252574Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-12-10T08:06:33Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
title |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
spellingShingle |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients Pietrobon, Anna Julia COVID-19 Trifosfato de adenosina Purinérgicos Adenosina 5'-nucleotidase Adenosine ATP CD39 CD73 COVID-19 SARS-CoV-2 Purinergic signaling |
title_short |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
title_full |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
title_fullStr |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
title_full_unstemmed |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
title_sort |
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
author |
Pietrobon, Anna Julia |
author_facet |
Pietrobon, Anna Julia Andrejew, Roberta Custódio, Ricardo Wesley Alberca Oliveira, Luana de Mendonça Scholl, Juliete Nathali Teixeira, Franciane Mouradian Emidio Brito, Cyro Alves de Glaser, Talita Kazmierski, Julia Goffinet, Christine Turdo, Anna Claudia Yendo, Tatiana Aoki, Valéria Figueiró, Fabrício Battastini, Ana Maria Oliveira Ulrich, Henning Benard, Gill Duarte, Alberto Jose da Silva Sato, Maria Notomi |
author_role |
author |
author2 |
Andrejew, Roberta Custódio, Ricardo Wesley Alberca Oliveira, Luana de Mendonça Scholl, Juliete Nathali Teixeira, Franciane Mouradian Emidio Brito, Cyro Alves de Glaser, Talita Kazmierski, Julia Goffinet, Christine Turdo, Anna Claudia Yendo, Tatiana Aoki, Valéria Figueiró, Fabrício Battastini, Ana Maria Oliveira Ulrich, Henning Benard, Gill Duarte, Alberto Jose da Silva Sato, Maria Notomi |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Pietrobon, Anna Julia Andrejew, Roberta Custódio, Ricardo Wesley Alberca Oliveira, Luana de Mendonça Scholl, Juliete Nathali Teixeira, Franciane Mouradian Emidio Brito, Cyro Alves de Glaser, Talita Kazmierski, Julia Goffinet, Christine Turdo, Anna Claudia Yendo, Tatiana Aoki, Valéria Figueiró, Fabrício Battastini, Ana Maria Oliveira Ulrich, Henning Benard, Gill Duarte, Alberto Jose da Silva Sato, Maria Notomi |
dc.subject.por.fl_str_mv |
COVID-19 Trifosfato de adenosina Purinérgicos Adenosina 5'-nucleotidase |
topic |
COVID-19 Trifosfato de adenosina Purinérgicos Adenosina 5'-nucleotidase Adenosine ATP CD39 CD73 COVID-19 SARS-CoV-2 Purinergic signaling |
dc.subject.eng.fl_str_mv |
Adenosine ATP CD39 CD73 COVID-19 SARS-CoV-2 Purinergic signaling |
description |
Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-12-09T04:58:49Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/252574 |
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1664-3224 |
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001155287 |
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1664-3224 001155287 |
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http://hdl.handle.net/10183/252574 |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in immunology. Lausanne. Vol. 13 (2022), 1012027, 12 p. |
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