Mechanistic insights from inflammasome structures

Nature reviews. Immunology, Год журнала: 2024, Номер 24(7), С. 518 - 535

Опубликована: Фев. 19, 2024

Язык: Английский

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Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6389 - 6389

Опубликована: Июнь 9, 2024

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase COVID-19. Characterized by myriad symptoms across different organ systems, LC presents significant diagnostic management challenges. Central disorder is role low-grade inflammation, non-classical inflammatory response that contributes chronicity diversity observed. This review explores pathophysiological underpinnings LC, emphasizing importance inflammation core component. By delineating pathogenetic relationships clinical manifestations this article highlights necessity for an integrated approach employs both personalized medicine standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding but inform development therapeutic strategies could be applicable chronic conditions with similar features.

Язык: Английский

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Induction of the Inflammasome by the SARS‐CoV‐2 Accessory Protein ORF9b, Abrogated by Small‐Molecule ORF9b Homodimerization Inhibitors

Journal of Medical Virology, Год журнала: 2025, Номер 97(2)

Опубликована: Фев. 1, 2025

ABSTRACT Viral accessory proteins play critical roles in viral escape from host innate immune responses and inflammatory pathogenesis. Here we show that the SARS‐CoV‐2 protein, ORF9b, but not other (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome‐dependent caspase‐1 A549 lung carcinoma cells THP‐1 monocyte‐macrophage cells. Exposure to lipopolysaccharide (LPS) ATP additively enhanced activation of by suggesting ORF9b LPS follow parallel pathways inflammasome caspase‐1. Following rational silico approaches, have designed small molecules capable inhibiting homodimerization which experimentally inhibited ORF9b‐ORF9b homotypic interactions, caused mitochondrial eviction ORF9b‐induced cells, cytokine release restored type I interferon (IFN‐I) signaling suppressed both cell models. These are first‐in‐class compounds targeting a protein for viral‐induced exacerbated inflammation responses, with potential mitigating severe immunopathogenic damage induced highly pathogenic coronaviruses restoring antiviral curtailed infection.

Язык: Английский

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Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Фев. 12, 2025

The emergence of the COVID-19 pandemic made it critical to understand immune and inflammatory responses SARS-CoV-2 virus. It became increasingly recognized that response was a key mediator illness severity its mechanisms needed be better understood. Early infection both tissue cells, such as macrophages, leading pyroptosis-mediated inflammasome production in an organ system for systemic oxygenation likely plays central role morbidity wrought by SARS-CoV-2. Delayed transcription Type I III interferons may lead early disinhibition viral replication. Cytokines interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor α (TNFα), some which produced through involving nuclear kappa B (NF-κB), contribute hyperinflammatory state patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) CD8+ T-cells, B-cells, can disease reflect direct cytopathic effects or end-organ sequestration. Direct activation endothelial cells mechanism systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation microthrombi development seen lungs other organs throughout body, heart, gut, brain. kidney most impacted extrapulmonary owing high concentration ACE2 exposure kidney, acute tubular injury, myofibroblast activation, collapsing glomerulopathy select populations account COVID-19-related AKI CKD development. COVID-19-associated nephropathy (COVAN), particular, mediated IL-6 signal transducer activator 3 (STAT3) signaling, suggesting connection between chronic disease. Chronic manifestations also include conditions like Multisystem Inflammatory Syndrome Children (MIS-C) Adults (MIS-A) post-acute sequelae (PASC), spectrum clinical presentations persistent dysregulation. lessons learned those undergoing continued study have broad implications understanding infections’ immunologic consequences beyond coronaviruses.

Язык: Английский

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Host mitochondria: more than an organelle in SARS-CoV-2 infection

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Авг. 25, 2023

Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. patients may present with wide range of symptoms, from asymptomatic to requiring intensive care support. The form is often marked an altered immune response and cytokine storm. Advanced age, age-related underlying diseases, including metabolic syndromes, appear contribute increased severity mortality suggesting role for mitochondria in pathogenesis. Furthermore, since system associated its damage-related molecular patterns (mtDAMPs), host mitochondrial play important during infections. Viruses have evolved modulate function survival proliferation, which turn could lead cellular stress progression. Recent studies focused on possible roles SARS-CoV-2 infection. It suggested that hijacking be key factor In this review, we discuss infections infection based past knowledge. Paying attention will help better understand pathophysiology achieve effective methods prevention, diagnosis, treatment.

Язык: Английский

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Differences and similarities between innate immune evasion strategies of human coronaviruses

Current Opinion in Microbiology, Год журнала: 2024, Номер 79, С. 102466 - 102466

Опубликована: Март 30, 2024

So far, seven coronaviruses have emerged in humans. Four recurring endemic cause mild respiratory symptoms. Infections with epidemic Middle East syndrome–related coronavirus or severe acute syndrome (SARS-CoV)-1 are associated high mortality rates. SARS-CoV-2 is the causative agent of disease 2019 pandemic. To establish an infection, evade restriction by human innate immune defenses, such as interferon system, autophagy and inflammasome. Here, we review similar distinct manipulation strategies employed coronaviruses. We further discuss impact on pathogenesis, zoonotic emergence adaptation. Understanding nature interplay between endemic/epidemic/pandemic host defenses may help to better assess pandemic potential emerging

Язык: Английский

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Innate immune mechanisms of infection: what we know and potential conserved mechanisms affecting sleep during infection

Neurobiology of Sleep and Circadian Rhythms, Год журнала: 2025, Номер unknown, С. 100121 - 100121

Опубликована: Апрель 1, 2025

Язык: Английский

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Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives

World Journal of Pediatrics, Год журнала: 2024, Номер 20(4), С. 307 - 324

Опубликована: Фев. 6, 2024

Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise the pediatric population with debilitating systemic impacts can be fatal at times, meriting further attention from clinicians. Meanwhile, intricate interactions between pathogen virulence factors host defense mechanisms are believed play indispensable roles COVID-19 pathophysiology but remain incompletely understood.

Язык: Английский

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Beyond acute infection: molecular mechanisms underpinning cardiovascular complications in long COVID

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Фев. 14, 2024

SARS-CoV-2, responsible for the global COVID-19 pandemic, has manifested significant cardiovascular implications infected population. These repercussions not only linger beyond initial phase of illness but have also been observed in individuals who remain asymptomatic. This extended and pervasive impact is often called post-acute syndrome (PACS) or “Long COVID”. With number confirmed cases approaching an alarming 756 million, multifaceted challenges Long COVID are undeniable. span from individual health complications to considerable burdens on worldwide healthcare systems. Our review comprehensively examines persistent associated with COVID-19. Furthermore, we shed light emerging therapeutic strategies that promise manage possibly mitigate these complications. We introduce discuss profound concerns regarding potential transgenerational emphasizing need a proactive informed approach future research clinical practice.

Язык: Английский

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Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3731 - 3731

Опубликована: Март 27, 2024

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation the inflammasome. Despite COVID-19 impact on public health, we still do not fully understand mechanisms by which inflammatory response influences prognosis. Accordingly, aimed to elucidate role polymorphisms in key genes formation and signaling inflammasome as biomarkers severity. For this purpose, a large well-defined cohort 377 patients mild (n = 72), moderate 84), severe 100), 121) infections were included. A total 24 located inflammasome-related (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, MIF) genotyped all 192 healthy controls (HCs) (who without at time before study) RT-qPCR. Our results showed that mild, moderate, severe, presented similar allelic genotypic distribution variants studied. No statistically significant differences haplotypic NLRP3, ATG16L1 observed between patients, who stratified Each group genetic HCs. In conclusion, our suggest studied worsening COVID-19.

Язык: Английский

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