Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/57629 |
Resumo: | Copyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotypeCOVID-19M2-like differentiationSARS-CoV-2Immune-regulationInnate immunityCopyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16- monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.The Research was funded by Fundação para a Ciência e Tecnologia (FCT), “APOIO ESPECIAL RESEARCH 4COVID-19” projects 803, 125, 231_596873172, and 729. AMCG and GF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD), and JANSSEN- CILAG FARMACÊUTICA, respectively. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of the article or decision to submit it for publication. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 667824.FrontiersRepositório da Universidade de LisboaTrombetta, Amelia ChiaraFarias, Guilherme B.Gomes, AndréGodinho-Santos, AnaRosmaninho, PedroConceição, Carolina M.Laia, JoelSantos, Diana F.Almeida, AfonsoMota, CatarinaGomes, AndreiaMontesinos Serrano, MartaVeldhoen, MarcSousa, Ana E.Fernandes, Susana M.2023-05-26T13:57:03Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57629engFront Immunol. 2021 Jun 23;12:69172510.3389/fimmu.2021.6917251664-3224info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:06:18Zoai:repositorio.ul.pt:10451/57629Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:08.520880Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| title |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| spellingShingle |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype Trombetta, Amelia Chiara COVID-19 M2-like differentiation SARS-CoV-2 Immune-regulation Innate immunity |
| title_short |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| title_full |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| title_fullStr |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| title_full_unstemmed |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| title_sort |
Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype |
| author |
Trombetta, Amelia Chiara |
| author_facet |
Trombetta, Amelia Chiara Farias, Guilherme B. Gomes, André Godinho-Santos, Ana Rosmaninho, Pedro Conceição, Carolina M. Laia, Joel Santos, Diana F. Almeida, Afonso Mota, Catarina Gomes, Andreia Montesinos Serrano, Marta Veldhoen, Marc Sousa, Ana E. Fernandes, Susana M. |
| author_role |
author |
| author2 |
Farias, Guilherme B. Gomes, André Godinho-Santos, Ana Rosmaninho, Pedro Conceição, Carolina M. Laia, Joel Santos, Diana F. Almeida, Afonso Mota, Catarina Gomes, Andreia Montesinos Serrano, Marta Veldhoen, Marc Sousa, Ana E. Fernandes, Susana M. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Trombetta, Amelia Chiara Farias, Guilherme B. Gomes, André Godinho-Santos, Ana Rosmaninho, Pedro Conceição, Carolina M. Laia, Joel Santos, Diana F. Almeida, Afonso Mota, Catarina Gomes, Andreia Montesinos Serrano, Marta Veldhoen, Marc Sousa, Ana E. Fernandes, Susana M. |
| dc.subject.por.fl_str_mv |
COVID-19 M2-like differentiation SARS-CoV-2 Immune-regulation Innate immunity |
| topic |
COVID-19 M2-like differentiation SARS-CoV-2 Immune-regulation Innate immunity |
| description |
Copyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2021-01-01T00:00:00Z 2023-05-26T13:57:03Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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publishedVersion |
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http://hdl.handle.net/10451/57629 |
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http://hdl.handle.net/10451/57629 |
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eng |
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eng |
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Front Immunol. 2021 Jun 23;12:691725 10.3389/fimmu.2021.691725 1664-3224 |
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info:eu-repo/semantics/openAccess |
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Frontiers |
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