Subcapsular sinus macrophages maximize germinal center development in non-draining lymph nodes during blood-borne viral infection

Science Immunology, Journal Year: 2024, Volume and Issue: 9(93)

Published: March 8, 2024

Lymph node (LN) germinal centers (GCs) are critical sites for B cell activation and differentiation. GCs develop after specialized CD169 + macrophages residing in LN sinuses filter antigens (Ags) from the lymph relay these Ags into proximal follicles. Many viruses, however, first reach LNs through blood during viremia (virus blood), rather than drainage infected tissue. How capture viral Ag to allow GC development is not known. Here, we followed Zika virus (ZIKV) dissemination mice subsequent formation both tissue–draining non-draining LNs. From footpad, ZIKV initially disseminated two chains, infecting leading formation. Despite rapid viremia, were several days. Non-draining infection correlated with virus-induced vascular leakage neutralization of permeability reduced macrophage attrition. Depletion significantly decreased cells nodes. Thus, although inefficiently captured directly blood, proceeded similarly draining sinus macrophages. Together, our findings reveal a conserved pathway allowing activate antiviral distal tissue blood-borne infection.

Language: Английский

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Changes and application prospects of biomolecular materials in small extracellular vesicles (sEVs) after flavivirus infection

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 15, 2025

Small extracellular vesicles (sEVs), also known as exosomes, are membranous filled with various proteins and nucleic acids, serving a communication vector between cells. Recent research has highlighted their role in viral diseases. This review synthesizes current understanding of sEVs includes recent findings on infected flaviviruses. It discusses the implications for advancing arbovirus anticipates potential applications flavivirus infections.

Language: Английский

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Extracellular Vesicles in Flaviviridae Pathogenesis: Their Roles in Viral Transmission, Immune Evasion, and Inflammation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2144 - 2144

Published: Feb. 10, 2024

The members of the Flaviviridae family are becoming an emerging threat for public health, causing increasing number infections each year and requiring effective treatment. consequences these can be severe include liver inflammation with subsequent carcinogenesis, endothelial damage hemorrhage, neuroinflammation, and, in some cases, death. mechanisms pathogenesis being actively investigated, but there still many gaps their understanding. Extracellular vesicles may play important roles mechanisms, therefore, this topic deserves detailed research. Recent data have revealed involvement extracellular steps such as transmission, immune evasion, inflammation, which is critical disease establishment. This review covers recent papers on includes examples clinical applications accumulated data.

Language: Английский

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Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible?

Published: July 10, 2024

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses prevalent alpha/ beta coronaviruses, but also Middle East Respiratory Syndrome (MERS-CoV) SARS-CoV-1, recent SARS–CoV–2 variants, increasing demands for effective immunogens therapeutic approaches that will reduce global burden further from SARS–CoV-2 affected individuals may experience post sequelae (PASC) or “Long COVID”. Following a worldwide programme prophylactic vaccination, there is still dilemma in efforts to find early would treat novel SARS-CoV-2 variants prevent future epidemics pandemics within host human animal populations, where zoonotic cross species transfer naturally occurs. Concerns about viral immune escape intersect at specific point; gained evolutionary ability several viruses co–infect compete against previous scientific advances since 1796 remain undetected asymptomatic during stages progressing symptomatic via double methylation 5' end eukaryotic DNA RNA-based genomes, 7-MeGpppA2’-O-Me cap, its capping process performed by activated 2’ - O Methyltransferase (MTase) enzyme, complex two non-structural proteins (NSPs) joined together through an activation (NSP10/16) N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered polymorphic translate NSP1, prevents various Pattern Recognition Receptors (PRRs), consequently, detection Pathogen-Associated Molecular Patterns (PAMPs) Damage-Associated (DAMPs) alike. NSP1 silences important interferon-encoding genes (INGs) interferon-stimulated (ISGs), signalled paracrine manner neighbouring cells, induces apoptosis inducing effect “trace erase” making as immunologically “invisible” possible initial, key replication distribution, all such mechanisms occurring independently cause. Another NSP NSP14, plays functional roles are independent each other; produce new genetic material purpose maintaining validity genome well, not just methyl group 5’ genome. Other NSPs share role 10, 14 16 directly suppressing PRRs ISGs, help virus self-camouflaging first- second-line immunity, thereby often severely impacting quality produced adaptive responses. outcome phenomena sharp decrease Type I III interferons' (IFNs) rate synthesis usually occur affect homeostatic cellular pathways, resulting induced apoptosis. Nonetheless, effects microbial evasion development carcinogenic pathologies widely known. In short, developed proportionate response responses, relying on gaps mostly situated natural system their molecular self-camouflaging. Scientists numerous treatment generally showed good success rates fewer risks adverse events, present COVID-19 research should be taken into consideration whilst filtering most appropriate solutions. For example, administration recombinant interferons nasal mucosa layer, mediators anti–viral activity, can simulate intracellular stimulate activity timely manner, training innate cells develop appropriately adequate B T cells. example could involve lymphocytes low dose IFNs possibly III, insertion lymphatic system, alongside additional recruitment plasmacytoid dendritic (pDCs) interferon “factories”, management. It might focusing offering information genetics protein structure pathogen, rather than first-line faster, excessively increases specificity, reach level brings opportunity evolve previously-developed mechanisms. until community realises this potentially crucial aspect large proportions world population probably continue face serious diseases over coming decades, evidenced dengue fever more recently, monkeypox avian flu. Of note, been indicated IFN / display significant immunising, clinical onset-attenuating many evoked diseases, well number oncological diseases.

Language: Английский

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Extracellular vesicles recovered from plasma of severe dengue patients induce CD4+ T cell suppression through PD-L1/PD-1 interaction

mBio, Journal Year: 2023, Volume and Issue: 14(6)

Published: Nov. 20, 2023

ABSTRACT Extracellular vesicles (EVs) are small membrane secreted into biological fluids, which play crucial roles in influencing the cellular function different pathological processes. However, there is less clarity on how plasma EVs influence proliferation activation and functions of immune cells during dengue virus (DV) infection. In this study, we aimed to characterize circulating from categories patients examined consequence naïve CD4+ T isolated mild or severe patients. We observed that infection was associated with an increased release CD41a+ platelet extracellular compared disease healthy donors. These carried level pro- anti-inflammatory cytokines along immunoregulatory proteins surface caused cell suppression. Treatment purified derived drove toward specific subtypes modulated receptor CXCR3 CCR6 expression. Subsequent studies indicated a notable rise programmed death ligand 1 (PD-L1) expression within DV (SDV) EVs. Additionally, showed elevated increase (PD-1) after incubating SDV-EVs. also demonstrated blocking PD-L1 SDV-EVs PD-1 late-activating CD4 + partially reversed SDV-EV-induced suppression proliferation. Overall, our study highlights immunosuppressive property patients, might contribute pathogenesis by shaping response. IMPORTANCE Severe manifestations global health problem. Studies suggest depends uncontrolled activation, excessive inflammation adds disease. Therefore, it important understand process triggers cells. The change response may be due direct virus-to-cell interaction could contact-independent through released infected importance context remains unexplored. understanding possible help delineate role progression Our present can have properties progression.

Language: Английский

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Dr Jekyll and Mr Hyde: From Two Branches of Immune Response to Three Types of Interferon Response

Published: Oct. 12, 2023

Interferons were the original prototype cytokine system discovered in 20th-century research. As name implies, they originally thought to be synthesised and secreted between cells. Thanks technological advances, processes involved protein secretion can explained comparatively more clearly at both genetic biochemical levels. The discovery of interferon (IFN) occurred when research was still its infancy. Franklin Wilkins structure function deoxyribonucleic acid (DNA) same time as Crick Watson; however, Isaacs Lindemann, two scientists, described first IFN 1957. Mutations caused by inherent synthesis during infection well within regulation pathways affecting cell proliferation. This remains central host effects through receptor subunits defined 6 domains. Type II is key immune a variety cells, mainly natural killer (NK) T Single–stranded and/or double–stranded RNA/DNA viruses, bacterial infections (e.g., _Escherichia coli_) fungal _Aspergillus_), also affect regulation. Pathogenic proteins utilise intra/extracellular that sense foreign antigens like Toll–like Receptors (TLRs), affected mutations human cellular transduction pathways. Since third type 2003, phenotypes further characterised, questions remain about immunological mechanisms contributing innate adaptive system. Alterations I/II/III IFNs differentially beneficially alter homeostatic pathological disease, with I being cancer Therefore, considered here are overall molecular, regulatory context developments.

Language: Английский

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[Review] The Landscape of Interferons in Health and Disease

Published: July 15, 2024

Interferons (IFNs) were the original prototype cytokine system discovered in 20th century research. As name interferon implies (derived from Latin interfere-on), these proteins have immunostimulatory, primarily antiviral and antitumour properties are synthesised secreted between cells. Due to technological advances, processes variable factors involved IFN regulation can be comparatively explained by expressed genes expressed. In this review, we provide a brief introduction background on history of We then an overview type I IFNs, associated cells, their receptors outline characteristics subtypes. distinguished three types immune higher mammals cellular signalling mechanisms IFNs together with IFN–inducible transmembrane (IFITM) during viral infection. Additionally, elucidated role diseases, as well II immunological disorders, infections deficiency followed Errors signal transduction activator transcription (STAT) protein pathway disease analysed. This paper concludes examination I/II/III since discovery timing synthesis within cell pathways, examining autoantibodies, interferons errors, finally closing current understanding immunotherapy cancer.

Language: Английский

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A Review Study of the Participation of Late Domains in Sorting and Transport of Viral Factors to Exosomes

Life, Journal Year: 2023, Volume and Issue: 13(9), P. 1842 - 1842

Published: Aug. 31, 2023

Cellular communication depends heavily on the participation of vesicular systems generated by most cells an organism. Exosomes play central roles in this process. Today, these vesicles have been characterized, and it has determined that cargo they transport is not within a random system. In fact, various molecular signals recruitment proteins participate biogenesis exosomes. It also shown multiple viruses can recruit to viral factors such as genomes or proteins. late domains present are critical for exosomal selection recognize introduce them into review, researchers discuss evidence related characterization their role exosome during infection.

Language: Английский

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Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 22, 2023

Introduction Zika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits prenatally exposed infants, with no clear understanding why some pregnancies are more severely affected. Differential control maternal ZIKV may explain the adverse outcomes. Methods Here, we investigated whether magnitude breadth ZIKV-specific antibody response is associated better virologic using rhesus macaque model prenatal infection. We inoculated 18 dams an Asian-lineage isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA infectious kinetics were determined over course pregnancy, as well burden maternal-fetal interface (MFI) delivery. Binding neutralizing assays performed to determine IgM IgG responses throughout along peptide microarray define linear epitopes recognized. Results Dams (n= 9) cleared detectable from plasma by 7 days post-infection (DPI) had lower MFI In comparison, worse still DPI but that persisted longer, higher The magnitudes significantly control, suggesting titers not Additionally, recognized did differ between Discussion Thus, do seem impact control. This be because first DPI, when present before robust generated. However, presence suggests these could used biomarker poor should explored further.

Language: Английский

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Exosomes in viral infection: Effects for pathogenesis and treatment strategies

Biocell, Journal Year: 2023, Volume and Issue: 47(12), P. 2597 - 2608

Published: Jan. 1, 2023

Exosomes are small vesicles that carry molecules from one cell to another. They have many features make them interesting for research, such as their stability, low immunogenicity, size of the nanoscale, toxicity, and selective delivery. can also interact with viruses in diverse ways. Emerging research highlights significant role exosomes viral infections, particularly context diseases like COVID-19, HIV, HBV HCV. Understanding intricate interplay between human immune system holds great promise development effective antiviral therapies. An important aspect is gaining clarity on how influence enhance infectivity through inherent characteristics. By leveraging innate properties exosomes, exploit machinery involved exosome biogenesis set replication, facilitate spread infection, eliminate responses. either help or hinder infection by modulating system. This review summarizes recent findings mediate they be used diagnosis therapy. could lead new clinical applications disease management.

Language: Английский

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