Africanized honeybee venom (Apis mellifera) promotes human complement activation split products storm DOI Creative Commons
Felipe Silva de França, Ricardo de Oliveira Orsi, Dayanne Carla Fernandes

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 13, 2024

Introduction Complement activation split products are signatures of many immunopathological disorders. Among the laboratory findings observed in these diseases, a reduction level circulating intact complement components can be mentioned, and this change has also been detected envenomation by multiple Africanized honeybee (Apis mellifera) stings. Although animals elicits diverse life-threatening reactions, capacity bee venom (AmV) to activate human system remains elusive. Methods By coupling immunochemical functional approaches, it was that AmV strongly consumes alternative pathway (AP) normal serum (NHS). Additionally, interfered with classical (CP) lectin pathways (LP) activities. In parallel, high increase Ba fragment levels detected, suggesting changes AP activity were due its activation. Furthermore, an C1s-C1INH complex decrease physiological MASP1-C1INH suggested CP LP activated presence AmV. Strikingly, NHS exposed increasing concentrations varying from 5 1000 µg/mL presented generation C3a, C4a C5a anaphylatoxins, sC5b-9 complexes assembly, thus reinforcing triggers Conclusion These results show is strong activator. This presents mixed profile, predominance suggests play important roles honeybee, as they could induce events patients may dictate patient clinical prognosis.

Язык: Английский

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease DOI Creative Commons
Felicity Liew, Claudia Efstathiou, Sara Fontanella

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(4), С. 607 - 621

Опубликована: Апрель 1, 2024

One in ten severe acute respiratory syndrome coronavirus 2 infections result prolonged symptoms termed long disease (COVID), yet phenotypes and mechanisms are poorly understood

Язык: Английский

Процитировано

43
Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID DOI Creative Commons

Kirsten Baillie,

Helen Davies,

Samuel Keat

и другие.

Med, Год журнала: 2024, Номер 5(3), С. 239 - 253.e5

Опубликована: Фев. 15, 2024

BackgroundLong COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with SARS-CoV-2. The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is hallmark acute COVID-19 but has not been investigated as potential determinant long COVID.MethodsWe quantified series complement proteins, including markers activation regulation, in plasma samples healthy convalescent confirmed history SARS-CoV-2 age/ethnicity/sex/infection/vaccine-matched patients COVID.FindingsMarkers classical (C1s-C1INH complex), alternative (Ba, iC3b), terminal pathway (C5a, TCC) were significantly elevated COVID. These combination had receiver operating characteristic predictive power 0.794. Other proteins regulators also quantitatively different between Generalized linear modeling further revealed clinically tractable just four these markers, namely the fragments iC3b, TCC, Ba, C5a, 0.785.ConclusionsThese findings suggest biomarkers could facilitate currently available inhibitors be used to treat COVID.FundingThis work was funded by National Institute for Health Research (COV-LT2-0041), PolyBio Foundation, UK Dementia Institute.

Язык: Английский

Процитировано

25
Pathophysiological mechanisms of thrombosis in acute and long COVID-19 DOI Creative Commons
Haijiao Jing, Xiaoming Wu, Mengqi Xiang

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 16, 2022

COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe mortality. disease is hyper-inflammatory response (cytokine storm) mediated by the immune system. However, role inflammatory in thrombosis remains incompletely understood. In this review, we investigate crosstalk between inflammation context COVID-19, focusing on contributions to pathogenesis propose combined use anti-inflammatory anticoagulant therapeutics. Under conditions, interactions neutrophils platelets, platelet activation, monocyte tissue factor expression, microparticle release, phosphatidylserine (PS) externalization as well complement activation collectively involved immune-thrombosis. Inflammation results apoptosis blood cells, leading release PS cells microparticles, which significantly enhances catalytic efficiency tenase prothrombinase complexes, promotes thrombin-mediated fibrin generation local clot formation. Given risk importance antithrombotic therapies has been generally recognized, but certain deficiencies treatment gaps remain. Antiplatelet drugs not combination treatments, thus fail dampen procoagulant activity. Current treatments also do an optimal time for anticoagulation. The efficacy depends therapy initiation. best early possible after diagnosis, ideally stage disease. We elaborate mechanisms long COVID complications, including persistent inflammation, endothelial injury dysfunction, coagulation abnormalities. above-mentioned contents provide therapeutic strategies further improve patient outcomes.

Язык: Английский

Процитировано

53
Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know DOI Creative Commons
Wioleta M. Zelek, R. A. Harrison

Immunobiology, Год журнала: 2023, Номер 228(3), С. 152393 - 152393

Опубликована: Май 1, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was identified in China 2019 as the causative agent of COVID-19, and quickly spread throughout world, causing over 7 million deaths, which occurred prior to introduction first vaccine. In following discussion, while recognising that complement is just one many players we focus on relationship between COVID-19 disease, with limited digression into directly-related areas such complement, kinin release, coagulation. Prior outbreak, an important role for diseases had been established. Subsequently, multiple investigations patients confirmed dysregulation likely be a major driver disease pathology, some, if not all, patients. These data fuelled evaluation complement-directed therapeutic agents small patient cohorts, claims significant beneficial effect. As yet, these early results have reflected larger clinical trials, posing questions who treat, appropriate time duration treatment, optimal target treatment. While control pandemic has achieved through global scientific medical effort comprehend etiology extensive SARS-CoV-2 testing quarantine measures, vaccine development, improved therapy, possibly aided by attenuation dominant strains, it yet over. this review, summarise complement-relevant literature, emphasise its main conclusions, formulate hypothesis involvement COVID-19. Based make suggestions how any future outbreak might better managed order minimise impact

Язык: Английский

Процитировано

29
SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling DOI Creative Commons
Luca Perico, Marina Morigi, Anna Pezzotta

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 14, 2023

The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect subunit 1 (S1) in inducing lung vascular damage and potential mechanisms contributing to injury. Here, we found that S1 injection mice transgenic for human angiotensin converting enzyme (ACE2) induced early loss thromboresistance at 3 days, as revealed by thrombomodulin von Willebrand factor (vWF) increase. In parallel, epithelial C3 deposits enhanced C3a receptor (C3aR) expression were observed. These changes preceded diffuse alveolar fibrin(ogen)/platelets aggregates 7 well inflammatory cell recruitment fibrosis. Treatment C3aR antagonist (C3aRa) inhibited accumulation C3a/C3aR activation, limiting thrombo-inflammation Our study demonstrates triggers dysfunction activates complement system, instrumental thrombo-inflammatory By extension, our data indicate C3aRa a valuable therapeutic strategy limit S1-dependent pathology.

Язык: Английский

Процитировано

19
Emerging role of complement in COVID-19 and other respiratory virus diseases DOI Creative Commons
Mark Xiao, Calder Ellsworth, Xuebin Qin

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Фев. 18, 2024

Abstract The complement system, a key component of innate immunity, provides the first line defense against bacterial infection; however, COVID-19 pandemic has revealed that it may also engender severe complications in context viral respiratory disease. Here, we review mechanisms activation and regulation explore their roles both protecting infection exacerbating We discuss emerging evidence related to complement-targeted therapeutics compare role other diseases like influenza syncytial virus. recent mechanistic studies animal models can be used for further investigation. Novel knockout are proposed better understand nuances system diseases.

Язык: Английский

Процитировано

8
Local complement activation and modulation in mucosal immunity DOI
Devesha H. Kulkarni, Marick Starick, Rafael Aponte Alburquerque

и другие.

Mucosal Immunology, Год журнала: 2024, Номер 17(4), С. 739 - 751

Опубликована: Июнь 4, 2024

Язык: Английский

Процитировано

7
C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps DOI Creative Commons

Bruna M. Silva,

Giovanni Freitas Gomes, Flávio P. Veras

и другие.

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(12)

Опубликована: Апрель 27, 2023

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved pathophysiology. signaling increased locally lung, especially neutrophils of critically ill patients compared influenza infection, as well lung tissue K18-hACE2 Tg mice (Tg mice) infected SARS-CoV-2. Genetic pharmacological inhibition C5aR1 ameliorated immunopathology Tg-infected mice. Mechanistically, found drives neutrophil extracellular traps-dependent (NETs-dependent) immunopathology. These data confirm role indicate antagonists useful for treatment.

Язык: Английский

Процитировано

17
Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target DOI Creative Commons
Zhangsheng Yang, Susannah E. Nicholson,

Tomas S. Cancio

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 17, 2023

The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, there an unmet demand pharmacologic therapies targeting the underlying pathology in patients suffering from illness. complement cascade (ComC) plays integral role regulation both innate adaptive immune responses. ComC activation can prime overzealous cytokine storm tissue/organ damage. lung injury (ALI) have established relationship with early maladaptive activation. In this review, we collected evidence current studies linking ALI/ARDS dysregulation, focusing on elucidating new emerging roles extracellular (canonical) intracellular (non-canonical or complosome), (complementome) pathobiology, highlighting complementome as a vital nexus pathobiological connectome via its crosstalking other systems immunome, DAMPome, PAMPome, coagulome, metabolome, microbiome. We also discussed diagnostic/therapeutic potential future direction care ultimate goal better defining mechanistic subtypes (endotypes theratypes) through methodologies order facilitate more precise effective complement-targeted therapy treating these comorbidities. This information leads support anti-inflammatory strategy by ComC, where arsenal clinical-stage complement-specific drugs available, especially due COVID-19.

Язык: Английский

Процитировано

13
The complement system: A key player in the host response to infections DOI Creative Commons
Archana Jayaraman, Sarah Walachowski, Markus Bosmann

и другие.

European Journal of Immunology, Год журнала: 2024, Номер 54(11)

Опубликована: Авг. 27, 2024

Abstract Infections are one of the most significant healthcare and economic burdens across world as underscored by recent coronavirus pandemic. Moreover, with increasing incidence antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions design effective treatment strategies. The complement system a key arsenal host defense response pathogens bridges both innate adaptive immunity. However, in contest between mechanisms, not always victorious. Pathogens have evolved several approaches, including co‐opting regulators evade complement‐mediated killing. Furthermore, deficiencies proteins, genetic therapeutic, can lead inefficient pathogen eradication, rendering more susceptible certain infections. On other hand, overwhelming infection provoke fulminant activation uncontrolled inflammation potentially fatal tissue organ damage. This review presents overview critical aspects complement‐pathogen during discusses perspectives on designing therapies mitigate dysfunction limit injury.

Язык: Английский

Процитировано

4