Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients

Detalhes bibliográficos
Autor(a) principal: Pietrobon, Anna Julia
Data de Publicação: 2022
Outros Autores: 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
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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spelling 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
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dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
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dc.language.iso.fl_str_mv eng
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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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