Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity
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 a...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2545 |
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| author | Jiram Torres-Ruiz Abdiel Absalón-Aguilar Miroslava Nuñez-Aguirre Alfredo Pérez-Fragoso Daniel Alberto Carrillo-Vázquez José Luis Maravillas-Montero Nancy R. Mejía-Domínguez Luis Llorente Beatriz Alcalá-Carmona Jaquelin Lira-Luna Carlos Núñez-Álvarez Guillermo Juárez-Vega David Meza-Sánchez Thierry Hernández-Gilsoul Miguel Tapia-Rodríguez Diana Gómez-Martín |
| author_facet | Jiram Torres-Ruiz Abdiel Absalón-Aguilar Miroslava Nuñez-Aguirre Alfredo Pérez-Fragoso Daniel Alberto Carrillo-Vázquez José Luis Maravillas-Montero Nancy R. Mejía-Domínguez Luis Llorente Beatriz Alcalá-Carmona Jaquelin Lira-Luna Carlos Núñez-Álvarez Guillermo Juárez-Vega David Meza-Sánchez Thierry Hernández-Gilsoul Miguel Tapia-Rodríguez Diana Gómez-Martín |
| author_sort | Jiram Torres-Ruiz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:39:24Z |
| format | Article |
| id | doaj.art-4f26e28e5c7f43fcb448ebdd21317f8c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:24Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4f26e28e5c7f43fcb448ebdd21317f8c2023-11-22T17:45:21ZengMDPI AGCells2073-44092021-09-011010254510.3390/cells10102545Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral AutoimmunityJiram Torres-Ruiz0Abdiel Absalón-Aguilar1Miroslava Nuñez-Aguirre2Alfredo Pérez-Fragoso3Daniel Alberto Carrillo-Vázquez4José Luis Maravillas-Montero5Nancy R. Mejía-Domínguez6Luis Llorente7Beatriz Alcalá-Carmona8Jaquelin Lira-Luna9Carlos Núñez-Álvarez10Guillermo Juárez-Vega11David Meza-Sánchez12Thierry Hernández-Gilsoul13Miguel Tapia-Rodríguez14Diana Gómez-Martín15Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoRed de Apoyo a la Investigacion, Coordinacion de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoRed de Apoyo a la Investigacion, Coordinacion de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoRed de Apoyo a la Investigacion, Coordinacion de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoRed de Apoyo a la Investigacion, Coordinacion de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoEmergency Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoMicroscopy Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoThe 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.https://www.mdpi.com/2073-4409/10/10/2545COVID-19SARS-CoV-2NETsLDGLL-37HMGB1 |
| spellingShingle | Jiram Torres-Ruiz Abdiel Absalón-Aguilar Miroslava Nuñez-Aguirre Alfredo Pérez-Fragoso Daniel Alberto Carrillo-Vázquez José Luis Maravillas-Montero Nancy R. Mejía-Domínguez Luis Llorente Beatriz Alcalá-Carmona Jaquelin Lira-Luna Carlos Núñez-Álvarez Guillermo Juárez-Vega David Meza-Sánchez Thierry Hernández-Gilsoul Miguel Tapia-Rodríguez Diana Gómez-Martín Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity Cells COVID-19 SARS-CoV-2 NETs LDG LL-37 HMGB1 |
| title | Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity |
| title_full | Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity |
| title_fullStr | Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity |
| title_full_unstemmed | Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity |
| title_short | Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity |
| title_sort | neutrophil extracellular traps contribute to covid 19 hyperinflammation and humoral autoimmunity |
| topic | COVID-19 SARS-CoV-2 NETs LDG LL-37 HMGB1 |
| url | https://www.mdpi.com/2073-4409/10/10/2545 |
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