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

Nature reviews. Immunology, Год журнала: 2021, Номер 22(1), С. 47 - 56

Опубликована: Ноя. 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.

Язык: Английский

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Factors leading to high morbidity and mortality of COVID‐19 in patients with type 2 diabetes

Journal of Diabetes, Год журнала: 2020, Номер 12(12), С. 895 - 908

Опубликована: Июль 16, 2020

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), novel coronavirus. Diabetes (mostly type diabetes mellitus, T2DM) and hyperglycemia are among the major comorbidities in patients with COVID-19 leading to poor outcomes. Reports show that at an increased risk for developing complications including distress syndrome, multi-organ failure, death. Here we explore potential mechanistic links could explain observed higher morbidity mortality this patient population. Patients T2DM have underlying level of inflammation associated obesity insulin resistance addition other hypertension, obesity, cardiovascular disease, dyslipidemia, being older. We review evidence factors lead elevated expression angiotensin-converting enzyme (ACE2) lungs tissues; ACE2 cellular "receptor" port viral entry. The preexisting chronic augmented inflammatory response infection increasing load leads extreme systemic immune ("cytokine storm") strongly severity COVID-19. Based on available evidence, it recommended panel experts safe but stringent control blood glucose, pressure, lipids be carried out T2DM, measures potentially serve decrease should these contract infection. Once occurs, then attention directed proper glycemic use frequent monitoring glucose levels.

Язык: Английский

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Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality

International Immunopharmacology, Год журнала: 2022, Номер 104, С. 108516 - 108516

Опубликована: Янв. 6, 2022

Язык: Английский

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What causes hidradenitis suppurativa ?—15 years after

Experimental Dermatology, Год журнала: 2020, Номер 29(12), С. 1154 - 1170

Опубликована: Окт. 15, 2020

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from 1st International Hidradenitis Suppurativa Research Symposium held March 30-April 2, 2006 Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get molecular heart HS pathogenesis, which can only be achieved by renaissance solid basic research, as key developing more effective therapy." (Kurzen et al. What causes suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that desired research progressing rapid steps and has developed deep roots among inflammatory diseases Dermatology beyond, recognized "the skin disease than healed". This anniversary 43 research-performing all around globe official journal European Foundation e.V. (EHSF e.V.) Foundation, Inc (HSF USA) summarizes evidence intense clinical experimental during last 15 aspects provides information developments come near future.

Язык: Английский

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Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июль 5, 2021

Early and persistent activation of complement is considered to play a key role in the pathogenesis COVID-19. Complement products orchestrate proinflammatory environment that might be critical for induction maintenance severe inflammatory response SARS-CoV-2 by recruiting cells cellular immune system sites infection shifting their state towards an phenotype. It precedes pathophysiological milestone events like cytokine storm, progressive endothelial injury triggering microangiopathy, further activation, causes acute respiratory distress syndrome (ARDS). To date, application antiviral drugs corticosteroids have shown efficacy early stages infection, but failed ameliorate disease severity patients who progressed COVID-19 pathology. This report demonstrates lectin pathway (LP) recognition molecules system, such as MBL, FCN-2 CL-11, bind S- N-proteins, with subsequent LP-mediated C3b C4b deposition. In addition, our results confirm underline N-protein binds directly LP- effector enzyme MASP-2 activates complement. Inhibition LP using inhibitory monoclonal antibody against effectively blocks activation. FACS analyses transfected HEK-293 expressing S protein robust LP-dependent deposition on cell surface which inhibited antibody. light present results, encouraging performance clinical candidate inhibitor Narsoplimab recently published trials, we suggest targeting provides unsurpassed window therapeutic treatment

Язык: Английский

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Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19

JCI Insight, Год журнала: 2021, Номер unknown

Опубликована: Янв. 14, 2021

Background. Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.

Язык: Английский

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NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 2, 2022

Infection with SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism COVID-19 immunopathy is recruitment activation neutrophils at infection site, which also predicts severity poor outcomes. The release neutrophil extracellular traps (NETs), occurring during a regulated form cell death known as NETosis, key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis NET generation have been observed in many patients, leading to unfavorable coagulopathy immunothrombosis. Moreover, excessive are now more widely recognized mediators additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes NET-producing (e.g., low-density granulocytes) explain biological importance NETs protein cargos COVID-19. addition, discuss mechanisms upregulating viral processes entry replication) well host pro-NET proinflammatory mediator release, platelet activation, autoantibody production). Furthermore, provide an update main findings immunothrombosis other COVID-19-related disorders, such aberrant immunity, neurological post syndromes including lung fibrosis, disorder, tumor progression, deteriorated chronic illness. Finally, address potential prospective treatment strategies target dysregulated formation via inhibition promotion degradation, respectively.

Язык: Английский

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Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics

Pharmacological Reviews, Год журнала: 2021, Номер 73(2), С. 792 - 827

Опубликована: Март 9, 2021

The complement system was discovered at the end of 19th century as a heat-labile plasma component that "complemented" antibodies in killing microbes, hence name "complement." Complement is also part innate immune system, protecting host by recognition pathogen-associated molecular patterns. However, multifunctional far beyond infectious defense. It contributes to organ development, such sculpting neuron synapses, promoting tissue regeneration and repair, rapidly engaging synergizing with number processes, including hemostasis leading thromboinflammation. double-edged sword. Although it usually protects host, may cause damage when dysregulated or overactivated, systemic inflammatory reaction seen trauma sepsis severe coronavirus disease 2019 (COVID-19). Damage-associated patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, transplant dysfunction) chronic neurologic rheumatic activate complement, thereby increasing damaging inflammation. Despite long list diseases potential for ameliorating modulation, only few rare are approved clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust trials. evidence pathogenetic driver many more common suggests an opportunity future therapy, which, however, requires trials; one ongoing example COVID-19 disease. current review aims discuss pathogenesis pharmacological strategies treat these complement-targeted therapies.

Significance Statement

host's defense friend from invading pathogens, maintaining homeostasis. sword, since overactivated becomes enemy, damage, failure, and, worst case, death. A acute candidates avoid complement-dependent ranging well established possible large patient groups like pandemic 2019.

Язык: Английский

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

Nature reviews. Immunology, Год журнала: 2022, Номер 23(6), С. 381 - 396

Опубликована: Дек. 19, 2022

Язык: Английский

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A guide to complement biology, pathology and therapeutic opportunity

Nature reviews. Immunology, Год журнала: 2023, Номер 24(2), С. 118 - 141

Опубликована: Сен. 5, 2023

Язык: Английский

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