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Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV
While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutro...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432506/ https://www.ncbi.nlm.nih.gov/pubmed/37587169 http://dx.doi.org/10.1038/s41598-023-40475-0 |
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author | Park, Juwon Dean, Logan S. Heckl, Jack Gangcuangco, Louie Mar Pedro, Te-Kie Tallquist, Michelle D. Seto, Todd B. Shiramizu, Bruce Chow, Dominic C. Shikuma, Cecilia M. |
author_facet | Park, Juwon Dean, Logan S. Heckl, Jack Gangcuangco, Louie Mar Pedro, Te-Kie Tallquist, Michelle D. Seto, Todd B. Shiramizu, Bruce Chow, Dominic C. Shikuma, Cecilia M. |
author_sort | Park, Juwon |
collection | PubMed |
description | While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV−) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry. We demonstrated higher plasma levels of CitH3 in PLWH compared to HIV- individuals. LDGs from PLWH had heightened CD66b, but reduced CD16 expression. The percentages and counts of CD10(+) LDGs were significantly decreased in PLWH. In addition, the CD16(Lo) LDG subsets were enriched in PLWH, compared to HIV− group, indicating that immature LDGs are increased in PLWH. Moreover, LDGs from PLWH exhibited significantly higher NET forming capacity. In summary, our study presents evidence that LDGs from PLWH on ART display an immature and altered phenotype with increased NET formation. Among PLWH, plasma NET levels as well as LDG parameters correlated with blood markers for inflammation and coagulation, suggesting that neutrophil activation and NETs may exert proinflammatory and coagulation effects. Our data provide insights into the pathologic role of LDGs at least in part mediated through NET formation in PLWH. |
format | Online Article Text |
id | pubmed-10432506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104325062023-08-18 Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV Park, Juwon Dean, Logan S. Heckl, Jack Gangcuangco, Louie Mar Pedro, Te-Kie Tallquist, Michelle D. Seto, Todd B. Shiramizu, Bruce Chow, Dominic C. Shikuma, Cecilia M. Sci Rep Article While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV−) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry. We demonstrated higher plasma levels of CitH3 in PLWH compared to HIV- individuals. LDGs from PLWH had heightened CD66b, but reduced CD16 expression. The percentages and counts of CD10(+) LDGs were significantly decreased in PLWH. In addition, the CD16(Lo) LDG subsets were enriched in PLWH, compared to HIV− group, indicating that immature LDGs are increased in PLWH. Moreover, LDGs from PLWH exhibited significantly higher NET forming capacity. In summary, our study presents evidence that LDGs from PLWH on ART display an immature and altered phenotype with increased NET formation. Among PLWH, plasma NET levels as well as LDG parameters correlated with blood markers for inflammation and coagulation, suggesting that neutrophil activation and NETs may exert proinflammatory and coagulation effects. Our data provide insights into the pathologic role of LDGs at least in part mediated through NET formation in PLWH. Nature Publishing Group UK 2023-08-16 /pmc/articles/PMC10432506/ /pubmed/37587169 http://dx.doi.org/10.1038/s41598-023-40475-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Park, Juwon Dean, Logan S. Heckl, Jack Gangcuangco, Louie Mar Pedro, Te-Kie Tallquist, Michelle D. Seto, Todd B. Shiramizu, Bruce Chow, Dominic C. Shikuma, Cecilia M. Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV |
title | Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV |
title_full | Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV |
title_fullStr | Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV |
title_full_unstemmed | Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV |
title_short | Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV |
title_sort | low-density granulocytes display immature cells with enhanced net formation in people living with hiv |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432506/ https://www.ncbi.nlm.nih.gov/pubmed/37587169 http://dx.doi.org/10.1038/s41598-023-40475-0 |
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