Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery
IntroductionWe have acquired significant knowledge regarding the pathogenesis of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). However, the underlying mechanisms responsible for disease recovery still need to be fully understood.MethodsTo gain insights into critical immune...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227873/full |
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| author | Yanina Luciana Mazzocco Yanina Luciana Mazzocco Gastón Bergero Gastón Bergero Sebastian Del Rosso Sebastian Del Rosso Natalia Eberhardt Natalia Eberhardt Claudia Sola Claudia Sola Héctor Alex Saka Héctor Alex Saka Sofía María Villada José Luis Bocco José Luis Bocco Maria Pilar Aoki Maria Pilar Aoki |
| author_facet | Yanina Luciana Mazzocco Yanina Luciana Mazzocco Gastón Bergero Gastón Bergero Sebastian Del Rosso Sebastian Del Rosso Natalia Eberhardt Natalia Eberhardt Claudia Sola Claudia Sola Héctor Alex Saka Héctor Alex Saka Sofía María Villada José Luis Bocco José Luis Bocco Maria Pilar Aoki Maria Pilar Aoki |
| author_sort | Yanina Luciana Mazzocco |
| collection | DOAJ |
| description | IntroductionWe have acquired significant knowledge regarding the pathogenesis of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). However, the underlying mechanisms responsible for disease recovery still need to be fully understood.MethodsTo gain insights into critical immune markers involved in COVID-19 etiopathogenesis, we studied the evolution of the immune profile of peripheral blood samples from patients who had recovered from COVID-19 and compared them to subjects with severe acute respiratory illness but negative for SARS-CoV-2 detection (controls). In addition, linear and clustered correlations between different parameters were determined.ResultsThe data obtained revealed a significant reduction in the frequency of inflammatory monocytes (CD14+CD16+) at hospital discharge vs. admission. Remarkably, nitric oxide (NO) production by the monocyte compartment was significantly reduced at discharge. Furthermore, interleukin (IL)-6 plasma levels were negatively correlated with the frequency of NO+CD14+CD16+ monocytes at hospital admission. However, at the time of hospital release, circulating IL-6 directly correlated with the NO production rate by monocytes. In line with these observations, we found that concomitant with NO diminution, the level of nitrotyrosine (NT) on CD8 T-cells significantly diminished at the time of hospital release. Considering that purinergic signaling constitutes another regulatory system, we analyzed the kinetics of CD39 and CD73 ectoenzyme expression in CD8 T-cells. We found that the frequency of CD39+CD8+ T-cells significantly diminished while the percentage of CD73+ cells increased at hospital discharge. In vitro, IL-6 stimulation of PBMCs from COVID-19 patients diminished the NT levels on CD8 T-cells. A clear differential expression pattern of CD39 and CD73 was observed in the NT+ vs. NT-CD8+ T-cell populations.DiscussionThe results suggest that early after infection, IL-6 controls the production of NO, which regulates the levels of NT on CD8 T-cells modifying their effector functions. Intriguingly, in this cytotoxic cell population, the expression of purinergic ectoenzymes is tightly associated with the presence of nitrated surface molecules. Overall, the data obtained contribute to a better understanding of pathogenic mechanisms associated with COVID-19 outcomes. |
| first_indexed | 2024-03-11T21:54:22Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T21:54:22Z |
| publishDate | 2023-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-0bb72ea6c552461c94d0e48ad4d0e6f92023-09-26T04:54:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12278731227873Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recoveryYanina Luciana Mazzocco0Yanina Luciana Mazzocco1Gastón Bergero2Gastón Bergero3Sebastian Del Rosso4Sebastian Del Rosso5Natalia Eberhardt6Natalia Eberhardt7Claudia Sola8Claudia Sola9Héctor Alex Saka10Héctor Alex Saka11Sofía María Villada12José Luis Bocco13José Luis Bocco14Maria Pilar Aoki15Maria Pilar Aoki16Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaServicio de Enfermedades Infecciosas, Hospital Privado Universitario de Córdoba, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, ArgentinaUniversidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, ArgentinaIntroductionWe have acquired significant knowledge regarding the pathogenesis of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). However, the underlying mechanisms responsible for disease recovery still need to be fully understood.MethodsTo gain insights into critical immune markers involved in COVID-19 etiopathogenesis, we studied the evolution of the immune profile of peripheral blood samples from patients who had recovered from COVID-19 and compared them to subjects with severe acute respiratory illness but negative for SARS-CoV-2 detection (controls). In addition, linear and clustered correlations between different parameters were determined.ResultsThe data obtained revealed a significant reduction in the frequency of inflammatory monocytes (CD14+CD16+) at hospital discharge vs. admission. Remarkably, nitric oxide (NO) production by the monocyte compartment was significantly reduced at discharge. Furthermore, interleukin (IL)-6 plasma levels were negatively correlated with the frequency of NO+CD14+CD16+ monocytes at hospital admission. However, at the time of hospital release, circulating IL-6 directly correlated with the NO production rate by monocytes. In line with these observations, we found that concomitant with NO diminution, the level of nitrotyrosine (NT) on CD8 T-cells significantly diminished at the time of hospital release. Considering that purinergic signaling constitutes another regulatory system, we analyzed the kinetics of CD39 and CD73 ectoenzyme expression in CD8 T-cells. We found that the frequency of CD39+CD8+ T-cells significantly diminished while the percentage of CD73+ cells increased at hospital discharge. In vitro, IL-6 stimulation of PBMCs from COVID-19 patients diminished the NT levels on CD8 T-cells. A clear differential expression pattern of CD39 and CD73 was observed in the NT+ vs. NT-CD8+ T-cell populations.DiscussionThe results suggest that early after infection, IL-6 controls the production of NO, which regulates the levels of NT on CD8 T-cells modifying their effector functions. Intriguingly, in this cytotoxic cell population, the expression of purinergic ectoenzymes is tightly associated with the presence of nitrated surface molecules. Overall, the data obtained contribute to a better understanding of pathogenic mechanisms associated with COVID-19 outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227873/fullCD39CD73nitric oxidecytokinesinflammatory monocytesSARS-CoV-2 |
| spellingShingle | Yanina Luciana Mazzocco Yanina Luciana Mazzocco Gastón Bergero Gastón Bergero Sebastian Del Rosso Sebastian Del Rosso Natalia Eberhardt Natalia Eberhardt Claudia Sola Claudia Sola Héctor Alex Saka Héctor Alex Saka Sofía María Villada José Luis Bocco José Luis Bocco Maria Pilar Aoki Maria Pilar Aoki Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery Frontiers in Immunology CD39 CD73 nitric oxide cytokines inflammatory monocytes SARS-CoV-2 |
| title | Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery |
| title_full | Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery |
| title_fullStr | Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery |
| title_full_unstemmed | Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery |
| title_short | Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery |
| title_sort | differential expression patterns of purinergic ectoenzymes and the antioxidative role of il 6 in hospitalized covid 19 patient recovery |
| topic | CD39 CD73 nitric oxide cytokines inflammatory monocytes SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227873/full |
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