Distinct developmental pathways from blood monocytes generate human lung macrophage diversity

Evren, Elza; Ringqvist, Emma; Tripathi, Kumar Parijat; Sleiers, Natalie; Rives, Inés Có; Alisjahbana, A; Gao, Yu; Sarhan, Dhifaf; Halle, Tor; Sorini, Chiara; Lepzien, Rico; Marquardt, Nicole; Michaëlsson, Jakob; Smed‐Sörensen, Anna; Botling, Johan; Karlsson, Mikael C. I.; Villablanca, Eduardo J.; Willinger, Tim

doi:10.1016/j.immuni.2020.12.003

Cited by 121 publications

(158 citation statements)

References 93 publications

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“…As expected, partition-based graph abstraction (PAGA) suggests transcriptional similarity between healthy circulating CD14 + monocytes and healthy BAL macrophages, in agreement with recent data demonstrating that BAL macrophages can arise from circulating CD14 + monocytes ( Fig. 2C ) 30 . However, there is a surprisingly greater transcriptional similarity between BAL macrophages and the expanded population of circulating C1QA/B/C + CD16 + monocytes in COVID-19 ( Fig.…”

Section: Resultssupporting

confidence: 91%

The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres

Stephenson¹,

Reynolds²,

Botting³

et al. 2021

Preprint

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The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effector:effector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.

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Section: Resultssupporting

confidence: 91%

The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres

Stephenson¹,

Reynolds²,

Botting³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…(Fig. 2c) 23 . In COVID-19, there was greater transcriptional similarity between BAL macrophages and circulating C1QA/B/C + CD16 + monocytes (Fig.…”

Section: Mononuclear Phagocytes and Hspc Changesmentioning

confidence: 97%

Single-cell multi-omics analysis of the immune response in COVID-19

Stephenson

Reynolds

Botting

et al. 2021

Nat Med

495

561

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Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

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“…A minor population of LMs is constituted by intravascular macrophages (111). As shown by Evren et al (121), lung vasculature contains not only patrolling CD14loCD16+ and extravasating CD14+ monocytes but also intravascular macrophages. Despite populating the same anatomical niche, intravascular macrophages are distinct from blood monocytes in terms of morphology, phenotype, and gene expression.…”

Section: Lung Macrophagesmentioning

confidence: 93%

“…Despite populating the same anatomical niche, intravascular macrophages are distinct from blood monocytes in terms of morphology, phenotype, and gene expression. Intravascular LMs are functionally related to red pulp macrophages of the spleen and Kupffer cells of the liver; they preferentially express genes involved in red blood cell turnover and iron metabolism (CD163, HMOX1, FTL, SLC40A1, SLC48A1) and genes related to leukocyte-endothelium adhesion (121).…”

Section: Lung Macrophagesmentioning

confidence: 99%

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The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome

et al. 2021

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Macrophages are cells that mediate both innate and adaptive immunity reactions, playing a major role in both physiological and pathological processes. Systemic SARS-CoV-2-associated complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia. These are predominantly effects of massive macrophage activation that collectively can be defined as macrophage activation syndrome. In this review we focus on the role of macrophages in COVID-19, as pathogenesis of the new coronavirus infection, especially in cases complicated by ARDS, largely depends on macrophage phenotypes and functionalities. We describe participation of monocytes, monocyte-derived and resident lung macrophages in SARS-CoV-2-associated ARDS and discuss possible utility of cell therapies for its treatment, notably the use of reprogrammed macrophages with stable pro- or anti-inflammatory phenotypes.

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Distinct developmental pathways from blood monocytes generate human lung macrophage diversity

Cited by 121 publications

References 93 publications

The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres

The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres

Single-cell multi-omics analysis of the immune response in COVID-19

The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome

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