Mucosal immune response in biology, disease prevention and treatment

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Язык: Английский

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Infection and transmission of SARS‐CoV‐2 depend on heparan sulfate proteoglycans

The EMBO Journal, Год журнала: 2021, Номер 40(20)

Опубликована: Сен. 12, 2021

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with binding to proteoglycans, which might be an additional mechanism neutralize infection. infection epithelial cells was blocked low molecular weight heparins (LMWH). Although dendritic (DCs) mucosal Langerhans (LCs) were not infected SARS-CoV-2, both DC subsets efficiently captured via transmitted virus ACE2-positive cells. human primary nasal pre-treatment LMWH. These data strongly suggest that are important facilitating transmission, support use LMWH prophylaxis

Язык: Английский

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Spike-heparan sulfate interactions in SARS-CoV-2 infection

Current Opinion in Structural Biology, Год журнала: 2022, Номер 76, С. 102439 - 102439

Опубликована: Июль 6, 2022

Recent biochemical, biophysical, and genetic studies have shown that heparan sulfate, a major component of the cellular glycocalyx, participates in infection SARS-CoV-2 by facilitating so-called open conformation spike protein, which is required for binding to ACE2. This review highlights involvement sulfate cycle argues there high degree coordination between host cell asparagine-linked glycans on enabling ACE2 subsequent infection. The discovery protein depends both viral provides insights into evolution, spread potential therapies its variants.

Язык: Английский

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Current concepts on Pseudomonas aeruginosa interaction with human airway epithelium

PLoS Pathogens, Год журнала: 2023, Номер 19(3), С. e1011221 - e1011221

Опубликована: Март 30, 2023

Pseudomonas aeruginosa is a major, but opportunistic, respiratory pathogen, which rarely infects healthy individuals, mainly due to the barrier effect of human airway epithelium (HAE). This review explores interaction P. with HAE and progression infection. The basolateral part epithelium, includes membrane epithelial cells basement membrane, inaccessible in normal tight epithelia intact junctions. We highlight how exploits weaknesses gain access epithelium. crucial initiate infection observed injured repairing or chronically remodeled during extrusion senescent cell multiplication renewal. subsequent adhesion bacteria cytotoxic action virulence factors, including toxins delivered by type 3 secretion system (T3SS), lead retractions death. Eventually, progressively reaches propagates radially through basal disseminate using twitching flagellar motility.

Язык: Английский

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The role of dendritic cells in COVID-19 infection

Emerging Microbes & Infections, Год журнала: 2023, Номер 12(1)

Опубликована: Март 22, 2023

The persistent pandemic of coronavirus disease in 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) currently poses a major infectious threat to public health around the world. COVID-19 is an characterized strong induction inflammatory cytokines, progressive lung inflammation, and potential multiple organs dysfunction. SARS-CoV-2 infection closely related innate immune system adaptive system. Dendritic cells (DCs), as "bridge" connecting immunity immunity, play many important roles viral diseases. In this review, we will pay special attention possible mechanism dendritic human transmission clinical progression diseases, well reduction dysfunction DCs infection, so understand immunological characteristics infection.

Язык: Английский

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Coreceptor functions of cell surface heparan sulfate proteoglycans

AJP Cell Physiology, Год журнала: 2022, Номер 322(5), С. C896 - C912

Опубликована: Март 23, 2022

Receptor-ligand interactions play an important role in many biological processes by triggering specific cellular responses. These are frequently regulated coreceptors that facilitate, alter, or inhibit signaling. Coreceptors work parallel with other and accessory molecules to coordinate receptor-ligand interactions. Cell surface heparan sulfate proteoglycans (HSPGs) function as unique because they can bind ligands receptors through their HS core protein motifs. HSPGs typically expressed abundance of the signaling and, thus, capable mediating initial binding cell surface. HSPG do not possess kinase domains intrinsic enzyme activities for most part, does directly stimulate intracellular Because these features, primarily Given widely conserved, likely serve fundamental functions preserve basic physiological processes. Indeed, support growth factors, morphogens, chemokines, extracellular matrix (ECM) components, microbial pathogens secreted virulence factors. Through interactions, regulate adhesion, proliferation, migration, differentiation, impact onset, progression, outcome pathophysiological processes, such development, tissue repair, inflammation, infection, tumorigenesis. This review seeks provide overview various mechanisms how coreceptors.

Язык: Английский

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Surface charge changes in spike RBD mutations of SARS-CoV-2 and its variant strains alter the virus evasiveness via HSPGs: A review and mechanistic hypothesis

Frontiers in Public Health, Год журнала: 2022, Номер 10

Опубликована: Авг. 24, 2022

With the COVID-19 pandemic continuing, more contagious SARS-CoV-2 variants, including Omicron, have been emerging. The mutations, especially those that occurred on spike (S) protein receptor-binding domain (RBD), are of significant concern due to their potential capacity increase viral infectivity, virulence, and breakthrough antibodies' protection. However, molecular mechanism involved in pathophysiological change mutations remains poorly understood. Here, we summarized 21 RBD human angiotensin-converting enzyme 2 (hACE2) and/or neutralizing binding characteristics. We found most which could surface positive charge or polarity, enhanced hACE2 affinity immune evasion. Based dependence electrostatic interaction epitope residue virus docking (like receptors antibodies) for its invasion, postulated polarity changes novel S affect antibodies. Thus, modeled mutant trimers RBD-hACE2 complexes calculated electrotactic distribution study changes. Meanwhile, emphasized heparan sulfate proteoglycans (HSPGs) might play an important role hACE2-mediated entry into cells. Those hypotheses provide some hints how enhance fitness evasion, may indicate ways drug design, next-generation vaccine development, antibody therapies.

Язык: Английский

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Myocardial Oedema as a Consequence of Viral Infection and Persistence—A Narrative Review with Focus on COVID-19 and Post COVID Sequelae

Viruses, Год журнала: 2024, Номер 16(1), С. 121 - 121

Опубликована: Янв. 14, 2024

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic removal disturbed during pathological processes leading to inflammation, but also hypoxia or due alterations vascular perfusion coagulability. degradation of the glycocalyx as main component endothelial barrier well pericyte disintegration results accumulation interstitial intracellular water. Moreover, dysfunction evokes an increase metabolic waste products, cytokines inflammatory cells space contributing oedema formation. This leads stiffness impaired contractility, eventually resulting cardiomyocyte apoptosis, remodelling fibrosis. following article reviews pathophysiological including myocarditis, ischaemia-reperfusion injury viral infections with special focus on pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications potential long-term effects persistence (long COVID), treatment options, are discussed.

Язык: Английский

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Seaweed-derived fucoidans and rhamnan sulfates serve as potent anti-SARS-CoV-2 agents with potential for prophylaxis

Carbohydrate Polymers, Год журнала: 2024, Номер 337, С. 122156 - 122156

Опубликована: Апрель 16, 2024

Язык: Английский

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Cyclophilin–CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 3, 2025

Monocytes and macrophages, as important constituents of the innate immune system, are equipped with multiple Toll-like-receptors (TLRs) to recognize invading pathogens, such SARS-CoV-2, mount an antiviral response. Nevertheless, their uncontrolled activation can lead hyperinflammation seen in severe COVID-19. Surprisingly, we observed that recombinant SARS-CoV-2 Spike (S) Nucleocapsid (N) proteins triggered only a weak proinflammatory response human peripheral blood monocytes. By employing THP-1 Jurkat NF-κB::eGFP reporter cell lines expressing specific TLRs, various TLR ligands blocking antibodies, determined surface including TLR2/1, TLR2/6 TLR4 do not play major role sensing. However, monocytes potently activated by replication-competent correlates viral uptake is monocytes, but lymphocytes. We show monocyte involves two distinct steps. Firstly, infects process independent S protein prime receptor angiotensin-converting enzyme 2. Instead, alternative CD147, which highly expressed on recognizes its well-known interaction partners cyclophilins A B incorporated into virions. Secondly, upon via cyclophilin-CD147 interaction, be inhibited CD147 antibodies or competition cyclophilin B, RNA recognized TLR7/8 endosomes, leading upregulation tumor necrosis factor (TNF), interleukin (IL)-1β IL-6, comprising core hyperinflammatory signature. Taken together, our data reveal novel mechanism how sense suggest targeting axis might beneficial alleviate overt myeloid-driven inflammation infection.

Язык: Английский

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