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Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevan...

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Autores principales: González-Casimiro, Carlos M., Arribas-Rodríguez, Elisa, Fiz-López, Aida, Casas, Javier, Gutiérrez, Sara, Tellería, Pablo, Novoa, Cristina, Rojo-Rello, Silvia, Tamayo, Eduardo, Orduña, Antonio, Dueñas, Carlos, Bernardo, David, Perdomo, German
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570012/
https://www.ncbi.nlm.nih.gov/pubmed/36232381
http://dx.doi.org/10.3390/ijms231911070
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author González-Casimiro, Carlos M.
Arribas-Rodríguez, Elisa
Fiz-López, Aida
Casas, Javier
Gutiérrez, Sara
Tellería, Pablo
Novoa, Cristina
Rojo-Rello, Silvia
Tamayo, Eduardo
Orduña, Antonio
Dueñas, Carlos
Bernardo, David
Perdomo, German
author_facet González-Casimiro, Carlos M.
Arribas-Rodríguez, Elisa
Fiz-López, Aida
Casas, Javier
Gutiérrez, Sara
Tellería, Pablo
Novoa, Cristina
Rojo-Rello, Silvia
Tamayo, Eduardo
Orduña, Antonio
Dueñas, Carlos
Bernardo, David
Perdomo, German
author_sort González-Casimiro, Carlos M.
collection PubMed
description Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4(+) and CD4(−)), and, to a lower extent, in B-cells from healthy controls. Notably, IDE’s surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE’s surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4(+) T-cells, and CD4(−) T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4(+) T-cells and CD4(−) T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.
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spelling pubmed-95700122022-10-17 Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge González-Casimiro, Carlos M. Arribas-Rodríguez, Elisa Fiz-López, Aida Casas, Javier Gutiérrez, Sara Tellería, Pablo Novoa, Cristina Rojo-Rello, Silvia Tamayo, Eduardo Orduña, Antonio Dueñas, Carlos Bernardo, David Perdomo, German Int J Mol Sci Article Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4(+) and CD4(−)), and, to a lower extent, in B-cells from healthy controls. Notably, IDE’s surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE’s surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4(+) T-cells, and CD4(−) T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4(+) T-cells and CD4(−) T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients. MDPI 2022-09-21 /pmc/articles/PMC9570012/ /pubmed/36232381 http://dx.doi.org/10.3390/ijms231911070 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
González-Casimiro, Carlos M.
Arribas-Rodríguez, Elisa
Fiz-López, Aida
Casas, Javier
Gutiérrez, Sara
Tellería, Pablo
Novoa, Cristina
Rojo-Rello, Silvia
Tamayo, Eduardo
Orduña, Antonio
Dueñas, Carlos
Bernardo, David
Perdomo, German
Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge
title Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge
title_full Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge
title_fullStr Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge
title_full_unstemmed Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge
title_short Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge
title_sort altered surface expression of insulin-degrading enzyme on monocytes and lymphocytes from covid-19 patients both at diagnosis and after hospital discharge
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570012/
https://www.ncbi.nlm.nih.gov/pubmed/36232381
http://dx.doi.org/10.3390/ijms231911070
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