The virulence antigen (LcrV) of pathogenic yersiniae "silences" macrophages against stimulation with the TLR2-agonist zymosan A in a CD14/TLR2-dependent fashion via IL-10 induction. This pathogenically important "silencing" resembles TLR tolerance phenomena; in these, pre-exposure to a primary tolerizing TLR-agonist renders macrophages unresponsive to stimulation with a secondary challenging TLR-agonist which may involve either the same (TLR homotolerance) or a different TLR (TLR heterotolerance) as the primary TLR-agonist. Here, we show that rLcrV induces TLR homo- and heterotolerance against TLR2- or TLR4-agonists both in human and murine macrophages, respectively. The underlying mechanism of LcrV-induced tolerance is most likely not due to changes in TLR2- or TLR4 expression, but involves LcrV-mediated IL-10 production, since LcrV-induced TLR homo- and heterotolerance is highly impaired in IL-10(-/-) macrophages. Moreover, the involvement of IL-10 in TLR tolerance induction seems to be a more general phenomenon as shown by experiments using different TLR-agonists in IL-10(-/-) macrophages. Since LcrV acts as a secreted protein upon macrophages without requiring direct cell contact, as shown in transwell assays, we propose that yersiniae exploit IL-10-involving TLR tolerance mechanisms by the virulence factor LcrV.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cellimm.2004.12.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells.
J Nanobiotechnology
January 2025
Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor "lymphocyte function-associated antigen-1" (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18).
View Article and Find Full Text PDFA Belgian physician-initiated trial investigating the LifeStream peripheral stent graft system for the treatment of complex TASC C and D iliac lesions.
J Cardiovasc Surg (Torino)
February 2025
Department of Vascular Surgery, AZ Sint Blasius, Dendermonde, Belgium.
Background: Due to the heterogeneity of literature findings, stent type selection for the endovascular treatment of complex aorto-iliac occlusive disease remains challenging. The BELSTREAM study, a physician-initiated, prospective, multicenter, single-arm study, aims to report the safety and efficacy of the balloon expandable LifeStream Peripheral Stent Graft System (BD, Tempe, Arizona, USA) for the treatment of complex TASC C and D aorto-iliac artery lesions.
Methods: Seventy patients and 133 lesions were included at six Belgian institutions.
Innovative epitopes in Protein-A an immuno-informatics approach to combat MDR-MRSA infections.
Front Cell Infect Microbiol
January 2025
Department of Haematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.
Background: Methicillin-resistant (MRSA) poses a significant challenge in clinical environments due to its resistance to standard antibiotics. Protein A (SpA), a crucial virulence factor of MRSA, undermines host immune responses, making it an attractive target for vaccine development. This study aimed to identify potential epitopes within SpA that could elicit robust immune responses, ultimately contributing to the combat against multidrug-resistant (MDR) MRSA.
View Article and Find Full Text PDFToll-like receptor 1/2 activation reduces immunoglobulin free light chain production by multiple myeloma cells in the context of bone marrow stromal cells and fibronectin.
PLoS One
January 2025
Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before.
View Article and Find Full Text PDFThe role of celastrol in inflammation and diseases.
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 PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!