Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection DOI Creative Commons
Martina Severa, Roberta A. Diotti, Marilena P. Etna

et al.

PLoS Pathogens, Journal Year: 2021, Volume and Issue: 17(9), P. e1009878 - e1009878

Published: Sept. 2, 2021

SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell tissue damage associated multi-organ failure. Here, early interaction between immune cells was investigated interrogating vitro human peripheral blood mononuclear (PBMC)-based experimental model. We found that, even absence of productive viral replication, virus mediates vigorous TLR7/8-dependent production both III IFNs cytokines chemokines, known to contribute storm observed COVID-19. Interestingly, we how virus-induced secreted PBMC enhances anti-viral infected lung epithelial cells, thus, inhibiting replication. This released plasmacytoid dendritic (pDC) via ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype inducing surface expression PD-L1 marker, feature producing cells. Coherently what vitro, asymptomatic subjects displayed similar very high serum level induction IFN-stimulated genes PBMC. Conversely, hospitalized with severe COVID-19 display low frequency circulating levels chemokines pro-inflammatory serum. study further shed light on events resulting from occurring confirmed ex vivo. These observations can improve our understanding contribution pDC/type axis regulation state patients.

Language: Английский

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19 DOI Creative Commons
Sarthak Sinha, Nicole L. Rosin, Rohit Arora

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 28(1), P. 201 - 211

Published: Nov. 15, 2021

Abstract Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects dexamethasone severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, bacterial was associated with expansion distinct neutrophil states characterized by interferon (IFN) prostaglandin signaling. Dexamethasone affected circulating neutrophils, altered IFN active downregulated interferon-stimulated genes activated IL-1R2 + neutrophils. expanded immunosuppressive immature neutrophils remodeled cellular interactions changing information receivers into providers. Male patients had higher proportions preferential steroid-induced expansion, potentially affecting outcomes. Our atlas (see ‘Data availability’ section) defines COVID-19-enriched molecular action develop targeted immunotherapies COVID-19.

Language: Английский

Citations

198
Immunology of SARS-CoV-2 infection in children DOI Open Access
Janet Chou, Paul G. Thomas, Adrienne G. Randolph

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 177 - 185

Published: Feb. 1, 2022

Language: Английский

Citations

147
Immune signatures underlying post-acute COVID-19 lung sequelae DOI Creative Commons
In Su Cheon, Chaofan Li, Young Min Son

et al.

Science Immunology, Journal Year: 2021, Volume and Issue: 6(65)

Published: Sept. 30, 2021

Respiratory tissue resident–like CD8 + T cells are associated with chronic lung sequelae post-acute COVID-19.

Language: Английский

Citations

145
Discovering dominant tumor immune archetypes in a pan-cancer census DOI Creative Commons
Alexis J. Combes, Bushra Samad, Jessica Tsui

et al.

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 184 - 203.e19

Published: Dec. 27, 2021

Language: Английский

Citations

118
The intersection of COVID-19 and autoimmunity DOI Open Access
Jason S. Knight, Roberto Caricchio, Jean‐Laurent Casanova

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(24)

Published: Oct. 28, 2021

Acute COVID-19, caused by SARS-CoV-2, is characterized diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute pathogenesis of severe COVID-19. Researchers working at intersection COVID-19 autoimmunity recently gathered an American Autoimmune Related Diseases Association Noel R. Rose Colloquium address current state knowledge regarding two important questions: Does established predispose COVID-19? And, same time, can SARS-CoV-2 trigger de novo autoimmunity? Indeed, work date demonstrated 10% 15% patients critical pneumonia exhibit autoantibodies against type I interferons, suggesting preexisting underlies disease in some patients. Other studies have identified functional following such as those promote thrombosis or antagonize cytokine signaling. These may arise a predominantly extrafollicular B cell response more prone generating autoantibody-secreting cells. This Review highlights understanding, evolving concepts, unanswered questions provided this unique opportunity determine mechanisms which viral be exacerbated by, even trigger, autoimmunity. The potential role post-acute sequelae also discussed.

Language: Английский

Citations

112
Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection DOI Creative Commons
Alberto Pérez‐Gómez, Joana Vitallé, Carmen Gasca‐Capote

et al.

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(9), P. 2128 - 2139

Published: July 21, 2021

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is deficit DC numbers and IFN-α production, which has been associated with disease severity. this work, we described that addition deficiency, several activation homing markers were altered acute patients, multiple inflammatory markers. Remarkably, previously hospitalized nonhospitalized patients remained decreased CD1c+ myeloid pDCs seven months after SARS-CoV-2 infection. Moreover, expression such as CD86 CD4 only restored while no restoration integrin β7 indoleamine 2,3-dyoxigenase (IDO) levels observed. These findings contribute better understanding immunological sequelae COVID-19.

Language: Английский

Citations

108
Single-Cell Analysis Reveals the Range of Transcriptional States of Circulating Human Neutrophils DOI Open Access
Gustaf Wigerblad, Qilin Cao, Stephen R. Brooks

et al.

The Journal of Immunology, Journal Year: 2022, Volume and Issue: 209(4), P. 772 - 782

Published: Aug. 15, 2022

Neutrophils are the most abundant leukocytes in human blood and essential components of innate immunity. Until recently, neutrophils were considered homogeneous transcriptionally inactive cells, but both concepts being challenged. Single-cell RNA sequencing (scRNA-seq) offers an unbiased view cells along a continuum transcriptional states. However, use scRNA-seq to characterize has proven technically difficult, explaining part paucity published single-cell data on neutrophils. We have found that modifications analysis pipeline, rather than existing chemistries, can significantly increase detection scRNA-seq. then applied modified pipeline study peripheral Our findings indicate circulating heterogeneous which be classified into one four clusters reproducible among healthy subjects. demonstrate shift from relatively immature (Nh0) through transitional phenotype (Nh1), two end points defined by either relative inactivity (Nh2) or high expression type I IFN-inducible genes (Nh3). Transitions states characterized specific transcription factors. By simultaneously measuring surface proteins intracellular transcripts at level, we show these subsets independent canonical commonly used define These provide new neutrophil heterogeneity, with potential implications for characterization health disease.

Language: Английский

Citations

91
Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC) DOI Creative Commons
Sindhu Mohandas, Prasanna Jagannathan, Timothy J. Henrich

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 26, 2023

With a global tally of more than 500 million cases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses key determinants severity and outcomes initial well subsequent PASC. The complexity innate adaptive in period requires in-depth mechanistic analyses identify specific molecular signals cell populations which promote PASC pathogenesis. In this review, we examine current literature on mechanisms dysregulation COVID-19 limited emerging data immunopathology While phases may share some parallel immunopathology, it is likely quite distinct heterogeneous, thus requiring large-scale longitudinal patients with without after an infection. By outlining knowledge gaps PASC, hope provide avenues for novel research directions will ultimately lead precision therapies restore healthy function patients.

Language: Английский

Citations

65
Strategies of neutrophil diversification DOI Open Access
Miguel Palomino‐Segura, Jon Sicilia, Iván Ballesteros

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 575 - 584

Published: March 23, 2023

Language: Английский

Citations

62
Single-cell immunology of SARS-CoV-2 infection DOI Open Access
Yuan Tian, Lindsay N. Carpp,

Helen E. R. Miller

et al.

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 40(1), P. 30 - 41

Published: Dec. 20, 2021

Language: Английский

Citations

104