FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation

Nature, Journal Year: 2022, Volume and Issue: 606(7914), P. 576 - 584

Published: April 6, 2022

Language: Английский

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Inflammasome activation in infected macrophages drives COVID-19 pathology

Nature, Journal Year: 2022, Volume and Issue: 606(7914), P. 585 - 593

Published: April 28, 2022

Language: Английский

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Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Cell, Journal Year: 2021, Volume and Issue: 185(3), P. 493 - 512.e25

Published: Dec. 28, 2021

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, it remains unclear whether T cells contribute disease pathology. Here, we combined single-cell transcriptomics proteomics with mechanistic studies assess pathogenic cell functions inducing signals. We identified highly activated CD16

Language: Английский

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Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses — are we our own worst enemy?

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(1), P. 47 - 56

Published: Nov. 26, 2021

Human coronaviruses cause a wide spectrum of disease, ranging from mild common colds to acute respiratory distress syndrome and death. Three highly pathogenic human — severe coronavirus (SARS-CoV), Middle East SARS-CoV-2 have illustrated the epidemic pandemic potential coronaviruses, better understanding their disease-causing mechanisms is urgently needed for rational design therapeutics. Analyses patients revealed marked dysregulation immune system in cases infection, there ample evidence that aberrant responses are typified by impaired induction interferons, exuberant inflammatory delayed adaptive responses. In addition, various viral proteins been shown impair interferon signalling induce inflammasome activation. This suggests disease associated with mediated both dysregulated host active interference. Here we discuss our current involved each these scenarios. this Perspective, Lok-Yin Roy Wong Stanley Perlman consider how 2 (SARS-CoV-2) related able drive immunopathology. They provide an overview coronavirus-derived molecules interfere key innate responses, including pathways complement, NF-κB activation, as well activation immunity.

Language: Английский

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Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(6), P. 381 - 396

Published: Dec. 19, 2022

Language: Английский

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Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(635)

Published: Jan. 18, 2022

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific acute respiratory syndrome 2 (SARS-CoV-2) were associated with progression from mild more COVID-19. To study biology IgG immune complexes, we developed an vivo model that revealed human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation lung. Afucosylated complexes isolated patients COVID-19 induced cytokine production and robust infiltration lung by cells. contrast antibody structures progression, elicited messenger RNA SARS-CoV-2 vaccines highly fucosylated enriched sialylation, both modifications reduce potential IgG. Vaccine-elicited did not promote response. These results show IgG-FcγR define distinct activities mediated protection against, or to,

Language: Английский

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Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study

PLoS Medicine, Journal Year: 2023, Volume and Issue: 20(1), P. e1004086 - e1004086

Published: Jan. 31, 2023

Background Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised were greater in-hospital death and how this changed over the pandemic. Methods findings included > = 19 years symptomatic community-acquired COVID-19 recruited ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. used logistic regression compare in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, comorbidities. Bayesian explore time. Between 17 January 2020 28 February 2022, we 156,552 eligible patients, whom 21,954 (14%) immunocompromised. In total, 29% ( n 6,499) 21% 28,608) died hospital. The odds elevated (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had same risk, example, on active treatment less likely their care escalated intensive 0.77, [0.7, 0.85], 0.001) ventilation 0.65, [0.56, 0.76], more die 2.0, [1.87, 2.15], Analyses adjusted socioeconomic comorbidities, vaccination status. As pandemic progressed, reduced slowly than This was particularly evident increasing age: probability reduction hospital being aged 50 69 88% men 83% women, those >80 99% 98% women. study is limited by a lack detailed drug data prior admission, including steroid doses, meaning that incorrectly categorised some immunocompetent. Conclusions remain from COVID-19. Targeted measures such additional vaccine monoclonal antibodies, nonpharmaceutical preventive interventions should continually encouraged patient group. Trial registration ISRCTN 66726260 .

Language: Английский

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mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 12, 2023

Background The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination. Objective However, impact these formats with unclear effects on long-term Ab response – including isotype, subclass, their type Fc glycosylation is less explored. Methods Here, we analyzed anti-S in blood serum saliva naïve non-hospitalized pre-infected subjects upon two vaccinations different mRNA- combinations up to day 270. Results We show that initially high mRNA vaccine-induced salivary IgG levels, particularly IgG1, markedly decrease over time approach lower levels induced vaccine. All three induced, contrary IgG1 sialylation galactosylation a was characterized by low latter being even below corresponding total level. Instead, mRNA, but not IgG4 subclass inhibitory effector functions. Furthermore, IgA decreased faster as compared vaccinees. Predictively, age correlated titers vaccines. higher galactosylation, sialylation, bisection respectively, all combinations. Conclusion In summary, study suggests comparable “adjuvant” potential newly glycosylation, reflected relatively generated long-lived plasma cell pool, whose induction might be driven recently described T H1 -driven B repeated immunization individuals increased proportion which influence Taken together, data shed light novel implications efficacy.

Language: Английский

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Effect of posttranslational modifications and subclass on IgG activity: from immunity to immunotherapy

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(8), P. 1244 - 1255

Published: July 6, 2023

Language: Английский

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Integrin-Dependent Cell–Matrix Adhesion in Endothelial Health and Disease

Circulation Research, Journal Year: 2023, Volume and Issue: 132(3), P. 355 - 378

Published: Feb. 2, 2023

The endothelium is a dynamic, semipermeable layer lining all blood vessels, regulating vessel formation and barrier function. Proper composition function of the endothelial are required for fluid homeostasis, clinical conditions characterized by disruption associated with severe morbidity high mortality rates. Endothelial properties regulated cell-cell junctions intracellular signaling pathways governing cytoskeleton, but recent insights indicate an increasingly important role integrin-mediated cell-matrix adhesion in regulation. Here, we discuss diseases disruption, provide overview complexes pathways, their crosstalk junctions, other receptors. We further present into adhesions developing mature/adult various vascular beds, how dynamic regulation turnover regulates (patho)physiological like angiogenesis, inflammation response to hemodynamic stress. Finally, as leak still lack direct treatment, focus on understanding may novel targets current translational challenges future perspectives.

Language: Английский

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