Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity
| Autor: | Beatriz Alcalá-Carmona, David E. Meza-Sánchez, Abdiel Absalón-Aguilar, Guillermo Juárez-Vega, Alfredo Pérez-Fragoso, Miroslava Nuñez-Aguirre, Miguel Tapia-Rodríguez, José L. Maravillas-Montero, Diana Gómez-Martín, Carlos A. Núñez-Álvarez, Luis Llorente, Jaquelin Lira-Luna, Jiram Torres-Ruiz, Daniel Alberto Carrillo-Vázquez, Nancy R. Mejía-Domínguez, Thierry Hernández-Gilsoul |
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| Rok vydání: | 2021 |
| Předmět: |
LDG
DNA-complex Anti-nuclear antibody Neutrophils QH301-705.5 medicine.medical_treatment ISG-15 Autoimmunity HMGB1 Extracellular Traps Monocytes Article Flow cytometry Cathelicidins medicine Humans Secretion HMGB1 Protein Biology (General) Ubiquitins Autoantibodies Inflammation Microscopy Confocal biology medicine.diagnostic_test SARS-CoV-2 Chemistry Autoantibody COVID-19 LL-37 NETs General Medicine Neutrophil extracellular traps Flow Cytometry Healthy Volunteers Immunity Humoral Cross-Sectional Studies Cytokine Antibodies Antinuclear Immunology biology.protein Cytokines DNase and autoimmunity Antibody Antimicrobial Cationic Peptides Granulocytes |
| Zdroj: | Cells, Vol 10, Iss 2545, p 2545 (2021) Cells Volume 10 Issue 10 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10102545 |
| Popis: | The coronavirus disease 2019 (COVID-19) is related to enhanced production of NETs, and autoimmune/autoinflammatory phenomena. We evaluated the proportion of low-density granulocytes (LDG) by flow cytometry, and their capacity to produce NETs was compared with that of conventional neutrophils. NETs and their protein cargo were quantified by confocal microscopy and ELISA. Antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and the degradation capacity of NETs were addressed in serum. MILLIPLEX assay was used to assess the cytokine levels in macrophages’ supernatant and serum. We found a higher proportion of LDG in severe and critical COVID-19 which correlated with severity and inflammatory markers. Severe/critical COVID-19 patients had higher plasmatic NE, LL-37 and HMGB1-DNA complexes, whilst ISG-15-DNA complexes were lower in severe patients. Sera from severe/critical COVID-19 patients had lower degradation capacity of NETs, which was reverted after adding hrDNase. Anti-NET antibodies were found in COVID-19, which correlated with ANA and ANCA positivity. NET stimuli enhanced the secretion of cytokines in macrophages. This study unveils the role of COVID-19 NETs as inducers of pro-inflammatory and autoimmune responses. The deficient degradation capacity of NETs may contribute to the accumulation of these structures and anti-NET antibodies are related to the presence of autoantibodies. |
| Databáze: | OpenAIRE |
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