SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels

Nature Cardiovascular Research, Journal Year: 2023, Volume and Issue: 2(10), P. 899 - 916

Published: Sept. 28, 2023

Abstract Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response severe acute respiratory syndrome 2 (SARS-CoV-2) infection likely contributes this risk, whether SARS-CoV-2 directly infects coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that viral RNA is detectable replicates in lesions taken at autopsy from COVID-19 cases. targeted plaque macrophages exhibited a stronger tropism arterial than adjacent perivascular fat, correlating macrophage infiltration levels. entry was cholesterol-loaded primary dependent, part, on neuropilin-1. induced robust cultured human vascular explants secretion of cytokines known trigger events. Our data establish vessels, inducing inflammation could increase long-term risk.

Language: Английский

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The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(9), P. 1008 - 1035

Published: May 22, 2024

Abstract Type I and III interferons (IFNs) are essential for antiviral immunity act through two different but complimentary pathways. First, IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire viral restriction factors. Second, innate adaptive immunity. Dysregulation IFN production can lead to severe immune system dysfunction. It is thus crucial identify characterize cellular sources IFNs, their effects, regulation promote beneficial effects limit detrimental which depend on nature infected or diseased tissues, as we will discuss. Plasmacytoid dendritic cells (pDCs) produce large amounts all subtypes during infection. pDCs resistant infection many viruses, inhibiting evasion mechanisms viruses that target downstream responses. Therefore, considered control infections establishment protective A thorough bibliographical survey showed that, in most infections, despite being major producers, actually dispensable host resistance, achieved multiple depending tissue. Moreover, primary responses only transiently affected absence pDCs. More surprisingly, be some autoimmune diseases. This makes conservation vertebrate evolution an enigma raises outstanding questions about role not also other diseases under physiological conditions.

Language: Английский

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Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 13, 2024

Introduction Global microplastic (MP) pollution is now well recognized, with humans and animals consuming inhaling MPs on a daily basis, growing body of concern surrounding the potential impacts human health. Methods Using mouse model mild COVID-19, we describe herein effects azide-free 1 μm polystyrene MP beads, co-delivered into lungs SARS-CoV-2 omicron BA.5 inoculum. The effect host response to infection was analysed using histopathology RNA-Seq at 2 6 days post-infection (dpi). Results Although reduced clearance from lung, virus titres viral RNA levels were not significantly affected by MPs, overt MP-associated clinical or histopathological changes observed. However, infected revealed that exposure suppressed innate immune responses dpi increased pro-inflammatory signatures dpi. cytokine profile showed significant correlation ‘cytokine release syndrome’ signature observed in some COVID-19 patients. Discussion findings are consistent recent finding can inhibit phagocytosis apoptotic cells via binding Tim4. They also add literature suggesting dysregulate inflammatory processes specific disease settings.

Language: Английский

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Ontogeny and Function of Plasmacytoid Dendritic Cells

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 347 - 373

Published: June 28, 2024

Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and ensuing production I interferon other soluble mediators, which orchestrate adaptive responses. We review several aspects pDC biology that have recently come to fore. discuss emerging questions regarding lineage affiliation origin pDCs argue these constitute an integral part lineage. emphasize specific function as sentinels virus infection, particularly their distinct response virus-infected cells. This essential evolutionary role has been important for control coronaviruses, demonstrated by recent COVID-19 pandemic. Finally, we highlight key contribution systemic lupus erythematosus, in therapeutic targeting currently underway.

Language: Английский

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The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(3)

Published: July 30, 2024

SUMMARY Human alphaherpesvirus 1 (HSV-1) is a highly successful neurotropic pathogen that primarily infects the epithelial cells lining orofacial mucosa. After primary lytic replication in oral, ocular, and nasal mucosal cells, HSV-1 establishes life-long latency neurons within trigeminal ganglion. Patients with compromised immune systems experience frequent reactivation of from latency, leading to virus entry sensory neurons, followed by anterograde transport at innervated surface. Although recurrent infection corneal surface rare, it can result chronic immuno-inflammatory condition called herpetic stromal keratitis (HSK). HSK leads gradual vision loss cause permanent blindness severe untreated cases. Currently, there no cure or vaccine prevent latent infections, posing significant clinical challenge managing preventing loss. The conventional management relies on anti-virals suppress replication, anti-inflammatory drugs (such as corticosteroids) provide symptomatic relief pain inflammation, surgical interventions more cases replace damaged cornea. However, each treatment strategy has limitations, such local systemic drug toxicities emergence anti-viral-resistant strains. In this review, we summarize factors involved pathogenesis highlight alternate therapeutic strategies for HSK. We also discuss potential immunoregulatory cytokines immunometabolism modulators promising therapies against emerging

Language: Английский

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Oncolytic virus and tumor-associated macrophage interactions in cancer immunotherapy

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Aug. 28, 2024

Abstract Oncolytic viruses (OV) are a promising strategy in cancer immunotherapy. Their capacity to promote anti-tumoral immunity locally raises hope that cancers unresponsive current immunotherapy approaches could be tackled more efficiently. In this context, tumor-associated macrophages (TAM) must considered because of their pivotal role immunity. Even though TAM tend inhibit responses, ability secrete pro-inflammatory cytokines and phagocytose cells can harnessed therapeutic OVs have the potential functions favor But parallel, induce OV clearance tumor, thereby limiting efficacy highlighting interaction between is double edge sword. Moreover, engineered were recently developed modulate specific such as phagocytic activity. The circulating monocytes deliver into tumor after intravenous administration also emerging. review, we will present TAM, functions, delivery tumor.

Language: Английский

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Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

Frontiers of Medicine, Journal Year: 2023, Volume and Issue: 17(6), P. 1080 - 1095

Published: Dec. 1, 2023

Language: Английский

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The role of epithelial-mesenchymal transition in pulmonary fibrosis: lessons from idiopathic pulmonary fibrosis and COVID-19

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 13, 2024

Despite the tremendous advancements in knowledge of pathophysiology and clinical aspects SARS-CoV-2 infection, still many issues remain unanswered, especially long-term effects. Mounting evidence suggests that pulmonary fibrosis (PF) is one most severe complications associated with COVID-19. Therefore, understanding molecular mechanisms behind its development helpful to develop successful therapeutic strategies. Epithelial mesenchymal transition (EMT) cell specific variants endothelial (EndMT) mesothelial (MMT) are physio-pathologic cellular reprogramming processes induced by several infectious, inflammatory biomechanical stimuli. Cells undergoing EMT acquire invasive, profibrogenic proinflammatory activities secreting extracellular mediators. Their activity has been implicated pathogenesis PF a variety lung disorders, including idiopathic (IPF) Aim this article provide an updated survey mechanisms, emphasis on EMT-related processes, genesis IFP

Language: Английский

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Plasmacytoid dendritic cell sensing of African swine fever virus–infected macrophages results in STING-dependent robust interferon-α production

The Journal of Immunology, Journal Year: 2025, Volume and Issue: 214(1), P. 130 - 140

Published: Jan. 1, 2025

Abstract While several African swine fever virus (ASFV)–encoded proteins potently interfere with the cGAS-STING (cyclic GMP-AMP synthetase–stimulator of interferon genes) pathway at different levels to suppress (IFN) type I production in infected macrophages, systemic IFN-α is induced during early stages AFSV infection pigs. The present study elucidates a mechanism by which such responses can be triggered, least vitro. We demonstrate that monocyte-derived macrophages (MDMs) ASFV genotype 2 strains highly efficient but immunologically silent respect IFN I, IFN-stimulated gene induction, and tumor necrosis factor production. Additionally, does not directly activate plasmacytoid dendritic cells (pDCs). However, coculturing pDCs ASFV-infected MDMs results strong pDC response characterized high factor. turn, promoted interleukin-1 receptor antagonist macrophages. Similar sensing other viruses, activation required integrin-mediated cognate interactions form an interferogenic synapse. Inhibitor studies indicated requires STING formation gap junctions. IL-4–polarized showed increased susceptibility, IFN-γ–polarized higher activation. Pretreatment IFN-β IFN-γ also enhanced highlighting influence immunological microenvironment. These findings suggest detected pigs may result

Language: Английский

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Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 19, 2025

Abstract Nucleic acids from both self- and non-self-sources act as vital danger signals that trigger immune responses. Critical illnesses such acute respiratory distress syndrome, sepsis, trauma ischemia lead to the aberrant cytosolic accumulation massive release of nucleic are detected by antiviral innate receptors in endosome or cytosol. Activation for deoxyribonucleic ribonucleic triggers inflammation, a major contributor morbidity mortality critically ill patients. In past decade, there has been growing recognition therapeutic potential targeting acid sensing critical care. This review summarizes current knowledge ischemia. Given extensive research on common pathological conditions like cancer, autoimmune disorders, metabolic disorders aging, we provide comprehensive summary beyond illness offer insights may inform its role conditions. Additionally, discuss strategies specifically target sensing. By examining sources, sensor activation function, well impact regulating these pathways across various diseases, highlight driving illness.

Language: Английский

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