Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery

Frontiers in Immunology

Immunology

Héctor Alex Saka¹  Yanina Luciana Mazzocco¹  Claudia Sola¹  Gastón Bergero¹  Sebastian Del Rosso¹  Natalia Eberhardt¹  José Luis Bocco¹  Maria Pilar Aoki¹  Sofía María Villada² 

[1] Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina;Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina;Servicio de Enfermedades Infecciosas, Hospital Privado Universitario de Córdoba, Córdoba, Argentina;

关键词: CD39;    CD73;    nitric oxide;    cytokines;    inflammatory monocytes;    SARS-CoV-2;    nitrotyrosine;   

DOI  :  10.3389/fimmu.2023.1227873

 received in 2023-05-23, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Mazzocco, Bergero, Del Rosso, Eberhardt, Sola, Saka, Villada, Bocco and Aoki