Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19

Nassir, Nasna; Tambi, Richa; Bankapur, Asma; Heialy, Saba Al; Karuvantevida, Noushad; Khansaheb, Hamda; Zehra, Binte; Begum, Ghausia; Hameid, Reem Abdel; Ahmed, Awab; Deesi, Zulfa; Alkhajeh, Abdulmajeed; Uddin, K. M. Furkan; Akter, Hosneara; Shabestari, Seyed Ali Safizadeh; Almidani, Omar; Islam, Abu Zafor Md. Touhidul; Gaudet, Mellissa; Kandasamy, Richard K.; Loney, Tom; Tayoun, Ahmad Abou; Nowotny, Norbert; Woodbury‐Smith, Marc; Rahman, Proton; Kuebler, Wolfgang M.; Hachim, Mahmood Yaseen; Casanova, Jean‐Laurent; Berdiev, Bakhrom K.; Alsheikh‐Ali, Alawi A.; Uddin, Mohammed

doi:10.1016/j.isci.2021.103030

Cited by 16 publications

(12 citation statements)

References 61 publications

(75 reference statements)

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“…Unfortunately, currently, there is no systematic classification of macrophage subtypes in emphysema or COPD. The single-cell sequencing study by Nassir et al in patients with critical COVID-19 is of significance, in which monocyte-derived alveolar macrophages were divided into two clusters and one macrophage subtype, labeled CCL3L1 and FCGR3B, was identified to be significantly upregulated in critical COVID-19 (31). Since the classification and function of macrophage subtypes in emphysema are not yet clear, many studies still refer to the classification of M1 and M2 subtypes (32,33), exerting pro-inflammatory and repairing functions, respectively.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD

Wang

Chen²,

Bai³

et al. 2022

Front. Immunol.

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ObjectiveTo study the tissue-infiltrating immune cells of the emphysema phenotype of chronic obstructive pulmonary disease (COPD) and find the molecular mechanism related to the development of emphysema to offer potential targets for more precise treatment of patients with COPD.MethodsCombined analyses of COPD emphysema phenotype lung tissue-related datasets, GSE47460 and GSE1122, were performed. CIBERSORT was used to assess the distribution of tissue-infiltrating immune cells. Weighted gene co-expression network analysis (WGCNA) was used to select immune key genes closely related to clinical features. Rt-qPCR experiments were used for the validation of key genes. Emphysema risk prediction models were constructed by logistic regression analysis and a nomogram was developed.ResultsIn this study, three immune cells significantly associated with clinical features of emphysema (FEV1 post-bronchodilator % predicted, GOLD Stage, and DLCO) were found. The proportion of neutrophils (p=0.025) infiltrating in the emphysema phenotype was significantly increased compared with the non-emphysema phenotype, while the proportions of M2 macrophages (p=0.004) and resting mast cells (p=0.01) were significantly decreased. Five immune-related differentially expressed genes (DEGs) were found. WGCNA and clinical lung tissue validation of patients with emphysema phenotype were performed to further screen immune-related genes closely related to clinical features. A key gene (SERPINA3) was selected and included in the emphysema risk prediction model. Compared with the traditional clinical prediction model (AUC=0.923), the combined prediction model, including SERPINA3 and resting mast cells (AUC=0.941), had better discrimination power and higher net benefit.ConclusionThis study comprehensively analyzed the tissue-infiltrating immune cells significantly associated with emphysema phenotype, including M2 macrophages, neutrophils, and resting mast cells, and identified SERPINA3 as a key immune-related gene.

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Section: Discussionmentioning

confidence: 99%

Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD

Wang

Chen²,

Bai³

et al. 2022

Front. Immunol.

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“…FCN1 was apt to assist and improve the inflammatory response of organism (31), which explained why asymptomatic patients had the mild or insignificant clinical symptoms. Furthermore, FCNR3B was specifically expressed in critical patients, and the immunoglobulin Fc receptor regulated the adaptive and innate immune responses, which was essential against infection and prevention of chronic inflammation and autoimmune diseases (32). NK and T cells were the immune effector cells against virus infection (33).…”

Section: Discussionmentioning

confidence: 99%

A Landscape Study on COVID-19 Immunity at the Single-Cell Level

et al. 2022

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Since 2019, the coronavirus (COVID-19) has outbroken continuously, spreading internationally and threatening the public health. However, it was unknown how the disorder at the single-cell level was associated with the pathogenesis of COVID-19. This study presented the disorders of macrophages, epithelial cells, CD8+ T cells, and natural killer (NK) cells at the single-cell level in the courses of COVID-19 and analyzed the immune response to cytokine storm. Compared with the healthy group, patients with COVID-19 had higher proportions of macrophages and lower proportions of T and NK cells, especially proportions of macrophages and epithelial cells with an increase during patients’ conditions from mild to severe. This study suggested that there were high levels of pro-inflammatory and chemokine expressions in cells of COVID-19 and analyzed cell subsets to explore its changes and pathways. It was worth noting that several subsets of macrophages, epithelial cells, CD8 T cells, and NK cells were involved in inflammation pathways, including interleukin-17 (IL-17) signaling pathway and tumor necrosis factor (TNF) signaling pathway. Moreover, the pathways interacting COVID-19 and cytokine receptor with each other were remarkably enriched. In addition, these cell subsets played important roles in inflammation, and their abnormal functions may cause COVID-19. In conclusion, this study provided an immune outlook for COVID-19 at the single-cell level and revealed different pathways in immune response of COVID-19 single cells.

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“…For example, studies by Grant et al ( 27 ) identified a slowly unfolding, spatially restricted alveolitis in patients infected with SARS-CoV-2 in which alveolar macrophages containing the virus and T cells form a positive feedback loop that drives a persistent alveolar inflammation. Other work identified an upregulation of specific macrophage ( 28 ) or T cell subsets such as CD16 + T cells that directly promote lung microvascular endothelial cell injury ( 29 ).…”

Section: Conceptual Barriersmentioning

confidence: 99%

ARDS in the time of corona: context and perspective

Voelkel

Bogaard

Kuebler

2022

American Journal of Physiology-Lung Cellular and Molecular Phys

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For more than two years, Covid-19 has been holding the world at awe with new waves of infections, novel mutants, and still limited (albeit improved) means to combat SARS-CoV-2 induced respiratory failure, the most common and fatal presentation of severe Covid-19. In the present perspective, we draw from the successes and - mostly - failures in previous ARDS work and the experiences from Covid-19 to define conceptual barriers that have so far hindered therapeutic breakthroughs in this deadly disease, and to open up new avenues of thinking and thus, ultimately of therapy.

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Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19

Cited by 16 publications

References 61 publications

Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD

Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD

A Landscape Study on COVID-19 Immunity at the Single-Cell Level

ARDS in the time of corona: context and perspective

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