Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 5037 - 5037

Published: May 5, 2024

Toll-like receptors (TLRs) are vital components of the innate immune system, serving as first line defense against pathogens by recognizing a wide array molecular patterns. This review summarizes critical roles TLRs in surveillance and disease pathogenesis, focusing on their structure, signaling pathways, implications various disorders. We discuss intricacies TLRs, including ligand specificity, cascades, functional consequences activation. The involvement infectious diseases, autoimmunity, chronic inflammation, cancer is explored, highlighting potential therapeutic targets. also examine recent advancements TLR research, such development specific agonists antagonists, application immunotherapy vaccine development. Furthermore, we address challenges controversies surrounding research outline future directions, integration computational modeling personalized medicine approaches. In conclusion, represent promising frontier medical with to significantly impact novel strategies for range diseases.

Language: Английский

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The interaction of innate immune and adaptive immune system

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Language: Английский

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An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012854 - e1012854

Published: Jan. 8, 2025

Long non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality immune systems that control virus infection. However, how lncRNAs engage responses during influenza A (IAV) infection remains unclear. Here, we show lncRNA USP30-AS1 is up-regulated by multiple different IAV subtypes and required for tuning inflammatory antiviral response in Genetically inactivation enhances viral protein synthesis growth. an interferon-stimulated gene, induction can be achieved JAK-STAT mediated signaling activation. The regulation independent its proximal protein-coding gene USP30 . In infection, deletion unleashes high systemic involving a broad range pro-inflammatory factors, suggesting as critical modulator Furthermore, established database providing well-annotated host expression profiles or stimulation.

Language: Английский

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Integrative multi-omics analysis reveals the role of toll-like receptor signaling in pancreatic cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

As one of the most destructive and invasive cancers, pancreatic cancer exhibits complex tumor heterogeneity, which has been a major challenge for clinicians in terms patient treatment prognosis. The toll-like receptor (TLR) pathway is closely related to immune microenvironment within various tissues. To explore development pattern find an ideal biomarker, our research explored mechanism TLR cancer. We collected single-cell expression data from 57,024 cells transcriptomic 945 patients, conducted series analyses at both levels. By calculating score, we clustered patients including metabolic pathways, microenvironment, drug sensitivity so on. In process building prognostic models, screened 33 core genes prognosis cancer, combined machine learning algorithms build model used single cell sequencing clarify intrinsic relationship between strongest signals were observed macrophages endothelial cells. With occurrence signal types gradually increased, but with increase malignant degree ductal epithelial cells, weakened. Cluster analysis showed that active had severe dysregulation worst Finally, includes four (NT5E, TGFBI, ANLN, FAM83A). strong performance predicting survival state samples. important role established validated new based on TLR-related genes.

Language: Английский

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The Role of TLRs in Obesity and Its Related Metabolic Disorders

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2229 - 2229

Published: March 1, 2025

Obesity affects the adaptability of adipose tissue (AT), impairing its ability to regulate energy and metabolism. is associated with many metabolic disorders, including dyslipidemia, hypertension, sleep non-alcoholic liver disease, some types cancer. Toll-like receptors (TLRs) are important in obesity related disorders. TLRs pattern-recognizing (PRRs) involved innate immune system recognize pathogen-associated molecular patterns (PAMPs) endogenous ligands. TLRs, especially TLR2 TLR4, activated by fatty acids, endotoxins, other TLR4 activation triggers inflammatory responses. Chronic inflammation driven TLR a hallmark diseases. The response triggered alters insulin signaling, contributing resistance, key feature syndrome type 2 diabetes. Modulation activity through lifestyle changes (diet exercise), surgery, pharmacological agents under study as possible therapeutic approach controlling complications.

Language: Английский

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HIV–Host Cell Interactions

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1351 - 1351

Published: May 9, 2023

The development of antiretroviral drugs (ARVs) was a great milestone in the management HIV infection. ARVs suppress viral activity host cell, thus minimizing injury to cells and prolonging life. However, an effective treatment has remained elusive for four decades due successful immune evasion mechanisms virus. A thorough understanding molecular interaction with cell is essential both preventive curative therapies This review highlights several inherent that promote its survival propagation, such as targeting CD4+ lymphocytes, downregulation MHC class I II, antigenic variation envelope complex minimizes antibody access, how they collaboratively render system unable mount response.

Language: Английский

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Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(8), P. 1671 - 1671

Published: Aug. 11, 2022

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines live-attenuated inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria confer long-term protection. review provides overview of protein-based (PBAs) obtained from different organisms, including bacteria, mollusks, plants, humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- T-cell-mediated immune responses administered antigens, providing advantages over many currently adopted adjuvant approaches. Furthermore, natural biocompatible biodegradable substances induce minimal reactogenicity toxicity interact innate receptors, enhancing their endocytosis modulating subsequent adaptive responses. We propose can contribute the development against complex pathogens, intracellular pathogens such as

Language: Английский

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Osteoimmunology in Periodontitis and Orthodontic Tooth Movement

Current Osteoporosis Reports, Journal Year: 2023, Volume and Issue: 21(2), P. 128 - 146

Published: March 2, 2023

Language: Английский

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Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 9818 - 9818

Published: June 6, 2023

The comprehensive anabolic effects of insulin throughout the body, in addition to control glycemia, include ensuring lipid homeostasis and anti-inflammatory modulation, especially adipose tissue (AT). prevalence obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on pandemic scale with accompanying syndemic health problems, including glucose intolerance, resistance (IR), diabetes. Impaired sensitivity or IR paradoxically leads diseases an inflammatory component despite hyperinsulinemia. Therefore, excess visceral AT obesity initiates chronic low-grade conditions that interfere signaling via receptors (INSRs). Moreover, response IR, hyperglycemia itself stimulates primarily defensive associated subsequent release numerous cytokines real threat organ function deterioration. In this review, all components vicious cycle are characterized particular emphasis interplay between both innate adaptive immune responses related obesity. Increased accumulation should be considered main environmental factor responsible for disruption epigenetic regulatory mechanisms system, resulting autoimmunity inflammation.

Language: Английский

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Acute lung injury caused by sepsis: how does it happen?

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 21, 2023

Sepsis is a systemic inflammatory disease caused by severe infections that involves multiple organs, among which the lung most susceptible, leaving patients highly vulnerable to acute injury (ALI). Refractory hypoxemia and respiratory distress are classic clinical symptoms of ALI sepsis, has mortality rate 40%. Despite extensive research on mechanisms exact pathological process not fully understood. This article reviews advances in pathogenesis sepsis focusing treatment regimens adopted practice for corresponding molecular mechanisms. review can only contribute theories but also recommend new strategies related injuries.

Language: Английский

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