Viral recognition and the antiviral interferon response

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(14)

Published: June 27, 2023

Language: Английский

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Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 123 - 123

Published: Jan. 9, 2024

The COVID-19 pandemic has brought to the forefront intricate relationship between SARS-CoV-2 and its impact on neurological complications, including potential links neurodegenerative processes, characterized by a dysfunction of protein quality control systems ER stress. This review article explores role systems, such as Unfolded Protein Response (UPR), Endoplasmic Reticulum-Associated Degradation (ERAD), Ubiquitin–Proteasome System (UPS), autophagy molecular chaperones, in infection. Our hypothesis suggests that produces stress exploits leading disruption proteostasis cannot be solved host cell. culminates cell death may represent link neurodegeneration.

Language: Английский

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Proinflammatory Cytokines in Chronic Respiratory Diseases and Their Management

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 400 - 400

Published: March 9, 2025

Pulmonary homeostasis can be agitated either by external environmental insults or endogenous factors produced during respiratory/pulmonary diseases. The lungs counter these initiating mechanisms of inflammation as a localized, non-specific first-line defense response. Cytokines are small signaling glycoprotein molecules that control the immune They formed numerous categories cell types and induce movement, growth, differentiation, death cells. During respiratory diseases, multiple proinflammatory cytokines play crucial role in orchestrating chronic structural changes tract recruiting inflammatory cells maintaining release growth to maintain inflammation. issue aggravates when response is exaggerated and/or cytokine production becomes dysregulated. In such instances, unresolving reactions accelerate airway remodeling maladaptive outcomes. Pro-inflammatory generate deleterious consequences through interactions with receptors, which turn initiate signal cell, triggering profile cascade seen different pulmonary diseases vary have become fundamental targets for advancement new therapeutic strategies lung There considerable approaches target cytokine-mediated diseases; however, blocking specific may not contribute clinical benefit. Alternatively, broad-spectrum anti-inflammatory more likely clinically effective. Herein, this comprehensive review literature identifies various (e.g., interleukins, chemokines, factors) involved pathogenesis asthma, obstructive pulmonary, cancer, pneumonia, fibrosis) investigates targeted treatment approaches.

Language: Английский

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Interference without interferon: interferon-independent induction of interferon-stimulated genes and its role in cellular innate immunity

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

ABSTRACT Interferons (IFNs) are multifaceted proteins that play pivotal roles in orchestrating robust antiviral immune responses and modulating the intricate landscape of host immunity. The major signaling pathway activated by IFNs is JAK/STAT (Janus kinase/signal transducer activator transcription) pathway, which leads to transcription a battery genes, collectively known as IFN-stimulated genes (ISGs). While well-established role coordinating innate response against viral infections widely acknowledged, recent years have provided more distinct comprehension functional significance attributed non-canonical, IFN-independent induction ISGs. In this review, we summarize non-conventional pathways ISG induction. These alternative offer new avenues for developing strategies or immunomodulation various diseases.

Language: Английский

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Investigating the Evolution of Drosophila STING-Dependent Antiviral Innate Immunity by Multispecies Comparison of 2′3′-cGAMP Responses

Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(3)

Published: Feb. 20, 2024

Viruses represent a major threat to all animals, which defend themselves through induction of large set virus-stimulated genes that collectively control the infection. In vertebrates, these include interferons play critical role in amplification response Virus- and interferon-stimulated restriction factors targeting different steps viral replication cycle, addition molecules associated with inflammation adaptive immunity. Predictably, antiviral evolve dynamically pressure. As result, each animal has unique arsenal genes. Here, we exploit capacity experimentally activate evolutionarily conserved stimulator IFN (STING) signaling pathway by injection cyclic dinucleotide 2'3'-cyclic guanosine monophosphate-adenosine monophosphate into flies define repertoire STING-regulated 10 Drosophila species, spanning 40 million years evolution. Our data reveal factors, including STING itself, cGAS-like-receptor, factor pastel, protein Vago, but also 2 key components RNA interference pathway, Dicer-2, Argonaute2. addition, identify unknown species- or lineage-specific have not been previously resistance viruses. provide insight core pave way for characterization effectors.

Language: Английский

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Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 6, 2024

Abstract Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression plays a crucial role in metastasis. Here, we solve this apparent paradox report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, resistance anoikis increasing glycolytic activity by sequestering miRNAs. Expression upregulates TRA2B splicing factor without affecting levels. Through transcriptional profiling, found downregulates through genes involved immune response. Analysis human colon samples showed an inverse correlation between CD8+ T infiltration, unveiling potential value as promising therapeutic target for tumors.

Language: Английский

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Comparative Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis: A Real‐World Multicentre Study in Japan

Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

ABSTRACT Background Three Janus kinase (JAK) inhibitors are approved for ulcerative colitis (UC) in Japan. Aim To compare the real‐world efficacy and safety of these three JAK UC. Methods This was a multicentre, retrospective study patients with UC started on inhibitors. The primary outcome clinical remission at 10, 26 58 weeks, most recent follow‐up. among inhibitors, we created matched cohorts (upadacitinib vs. filgotinib, tofacitinib filgotinib upadacitinib tofacitinib) using propensity score matching. Results We identified 228 upadacitinib‐treated (median follow‐up 49 weeks; IQR 25–72), 215 filgotinib‐treated (follow‐up 56 17–82) 159 tofacitinib‐treated 112 10–258). Clinical rates upadacitinib, were 72.8%, 50.6% 45.8%, respectively. Over 70% previously treated other biologics or achieved upadacitinib. On multivariate analysis, number previous advanced therapies inversely associated tofacitinib. Comparative analysis showed that had higher lower risk discontinuation than However, significant acne. Conclusions Considering particularly high even refractory UC, may be considered as an upfront inhibitor before

Language: Английский

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Role of type-I and type-III interferons in gastrointestinal homeostasis and pathogenesis

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 86, P. 102412 - 102412

Published: Feb. 1, 2024

Language: Английский

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cGAS-like receptors drive a systemic STING-dependent host response in Drosophila

Cell Reports, Journal Year: 2024, Volume and Issue: 43(12), P. 115081 - 115081

Published: Dec. 1, 2024

cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation vivo. Four tissues strongly respond injection cyclic dinucleotide 3'2'- guanosine monophosphate-adenosine monophosphate (cGAMP): central nervous system, midgut, Malpighian tubules, and genital ducts. The pattern induction injected with 3'2'-cGAMP or infected by two viruses different tropism suggests that is induced a systemic signal produced virus-infected cells. Accordingly, ectopic expression cGLR2 fat body induces STING signaling remote cGLR1/2-dependent activity transferred females during mating. Furthermore, infection can alter sleep cGLR1/2- STING-dependent manner. Altogether, our results reveal host response Drosophila.

Language: Английский

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Role of HIF in fish inflammation

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 143, P. 109222 - 109222

Published: Nov. 12, 2023

Language: Английский

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