Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients
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 verifi...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012027/full |
| _version_ | 1811207657929834496 |
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| author | Anna Julia Pietrobon Anna Julia Pietrobon Roberta Andrejew Ricardo Wesley Alberca Custódio Luana de Mendonça Oliveira Luana de Mendonça Oliveira Juliete Nathali Scholl Franciane Mouradian Emidio Teixeira Franciane Mouradian Emidio Teixeira Cyro Alves de Brito Talita Glaser Julia Kazmierski Julia Kazmierski Christine Goffinet Christine Goffinet Anna Claudia Turdo Tatiana Yendo Valeria Aoki Fabricio Figueiró Ana Maria Battastini Henning Ulrich Gill Benard Alberto Jose da Silva Duarte Maria Notomi Sato |
| author_facet | Anna Julia Pietrobon Anna Julia Pietrobon Roberta Andrejew Ricardo Wesley Alberca Custódio Luana de Mendonça Oliveira Luana de Mendonça Oliveira Juliete Nathali Scholl Franciane Mouradian Emidio Teixeira Franciane Mouradian Emidio Teixeira Cyro Alves de Brito Talita Glaser Julia Kazmierski Julia Kazmierski Christine Goffinet Christine Goffinet Anna Claudia Turdo Tatiana Yendo Valeria Aoki Fabricio Figueiró Ana Maria Battastini Henning Ulrich Gill Benard Alberto Jose da Silva Duarte Maria Notomi Sato |
| author_sort | Anna Julia Pietrobon |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T04:08:33Z |
| format | Article |
| id | doaj.art-5d0fb521e6ac4cd98c36ee04cf11d783 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T04:08:33Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5d0fb521e6ac4cd98c36ee04cf11d7832022-12-22T03:48:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.10120271012027Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patientsAnna Julia Pietrobon0Anna Julia Pietrobon1Roberta Andrejew2Ricardo Wesley Alberca Custódio3Luana de Mendonça Oliveira4Luana de Mendonça Oliveira5Juliete Nathali Scholl6Franciane Mouradian Emidio Teixeira7Franciane Mouradian Emidio Teixeira8Cyro Alves de Brito9Talita Glaser10Julia Kazmierski11Julia Kazmierski12Christine Goffinet13Christine Goffinet14Anna Claudia Turdo15Tatiana Yendo16Valeria Aoki17Fabricio Figueiró18Ana Maria Battastini19Henning Ulrich20Gill Benard21Alberto Jose da Silva Duarte22Maria Notomi Sato23Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilTechnical Division of Medical Biology, Immunology Center, Adolfo Lutz Institute, São Paulo, BrazilDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, BrazilInstitute of Virology, Charité - Universitätsmedizin Berlin, Berlin, GermanyDepartment and Division of Infectious and Parasitic Diseases, Berlin Institute of Health, Berlin, GermanyInstitute of Virology, Charité - Universitätsmedizin Berlin, Berlin, GermanyDepartment and Division of Infectious and Parasitic Diseases, Berlin Institute of Health, Berlin, GermanyDepartment and Division of Infectious and Parasitic Diseases, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, BrazilDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilLaboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, BrazilEctonucleotidases 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012027/fulladenosineATPCD39CD73COVID-19SARS-CoV-2 |
| spellingShingle | Anna Julia Pietrobon Anna Julia Pietrobon Roberta Andrejew Ricardo Wesley Alberca Custódio Luana de Mendonça Oliveira Luana de Mendonça Oliveira Juliete Nathali Scholl Franciane Mouradian Emidio Teixeira Franciane Mouradian Emidio Teixeira Cyro Alves de Brito Talita Glaser Julia Kazmierski Julia Kazmierski Christine Goffinet Christine Goffinet Anna Claudia Turdo Tatiana Yendo Valeria Aoki Fabricio Figueiró Ana Maria Battastini Henning Ulrich Gill Benard Alberto Jose da Silva Duarte Maria Notomi Sato Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients Frontiers in Immunology adenosine ATP CD39 CD73 COVID-19 SARS-CoV-2 |
| title | 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_short | Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients |
| title_sort | dysfunctional purinergic signaling correlates with disease severity in covid 19 patients |
| topic | adenosine ATP CD39 CD73 COVID-19 SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012027/full |
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