Abstract
Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4 + CD25 + CD39 + (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27 – CD28 – ) CD8 + T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4 + CD39 + , CD4 + CD25 – CD39 + (memory T effector cell), and high-differentiated CD8 + T cells (CD27 – CD28 – ), and diminished frequencies of CD4 + CD73 + , CD4 + CD25 + CD39 + mTreg cell, CD8 + CD73 + , and low-differentiated CD8 + T cells (CD27 + CD28 + ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8 + T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4 + Annexin-V + and CD8 + Annexin-V + T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4 + and CD8 + T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation.
Keywords: ATP; SARS-CoV-2; T lymphocytes; adenosine; inflammation; purines.
【저자키워드】 SARS-CoV-2, Inflammation, T lymphocytes, ATP, adenosine, purines., 【초록키워드】 COVID-19, coronavirus disease, Monocytes, Apoptosis, Coronavirus disease 2019, Cytokines, T cells, knowledge, triphosphate, cytokine, immunopathology, in vitro, CD4, CD8, viral infections, PD-1, Peripheral blood, Regulatory, T cell, Viral, Regulatory T cell, Immunopathogenesis, pathway, immune function, T lymphocytes, T-cell, expression, patients, CD25, adenosine, Blood, CD27, Signaling, Frequency, CD73, COVID-19 patient, mononuclear cell, adenosine triphosphate, Activation, Regulation, These data, alteration, plasma samples, severe COVID-19 patients, healthy controls, mild COVID-19 patients, CD28, purines, memory T, nuclear, Annexin, controls, Cell, decrease, healthy donor, Extracellular, collected, involved, reduced, modulate, effector cell, mild COVID-19 patient, Purinergic, severe COVID-19 patient, 【제목키워드】 severity, alteration, with COVID-19,