Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host's defense against infectious diseases, autoimmune diseases, and cancer.
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http://dx.doi.org/10.3389/fimmu.2022.812774 | DOI Listing |
Inflamm Res
January 2025
Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, Henan, China.
Celastrol is one of the main active ingredients extracted from the plant Tripterygium wilfordii Hook F. A growing number of studies have shown that celastrol has various pharmacological effects, including anti-inflammation, anti-rheumatism, treatment of neurodegenerative diseases, and anti-tumor. This article systematically summarized the mechanism and role of celastrol in lipid metabolism and obesity, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, inflammatory bowel disease, neurodegenerative diseases, and cancer and other diseases (such as diabetes, respiratory-related diseases, atherosclerosis, psoriasis, hearing loss, etc.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Endosomal toll-like receptors (TLRs) TLR7, TLR8, and TLR9 play an important role in systemic lupus erythematosus (SLE) pathogenesis. The proteolytic processing of these receptors in the endolysosome is required for signaling in response to DNA and single-stranded RNA, respectively. Targeting this proteolytic processing may represent a novel strategy to inhibit TLR-mediated pathogenesis.
View Article and Find Full Text PDFAntioxidants (Basel)
January 2025
Department of Functional Sciences, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
The absence of efficient on-farm interventions against white spot syndrome viral (WSSV) infections can cause significant economic losses to shrimp farmers. With this exploratory study we aimed to test, both in vitro and in vivo, the efficacy of an organic acid mixture (Aq) against WSSV infections in shrimp. In vitro, using shrimp gut primary cells (SGP), 2% Aq significantly reduced WSSV infection and the amounts of HO released but had no impact on CAT and SOD expression.
View Article and Find Full Text PDFJ Anim Sci Biotechnol
January 2025
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China.
Background: It is important to promote intestinal development and maturation of chicks for feed digestion and utilization, intestinal health, and disease resistance. This study aimed to investigate the effects of dietary yeast cell wall polysaccharides (YCWP) addition on intestinal development and maturation of chickens and its potential action mechanism.
Methods: 180 one-day-old male Arbor Acres broilers were randomly assigned to three groups containing control (basal diets without any antibiotics or anticoccidial drug), bacitracin methylene disalicylate (BMD)-treated group (50 mg/kg) and YCWP-supplemented group (100 mg/kg).
Nat Commun
January 2025
Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, the activation of IRF5 downstream of human TLR7, TLR8 and TLR9, but the pathophysiological functions of this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block of TLR7/9-induced IRF5 activation, while loss of TASL leads to a strong but incomplete impairment, which depends on the cell type and TLR engaged.
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