Asp(299)Gly (D299G) and, to a lesser extent, Thr(399)Ile (T399I) TLR4 polymorphisms have been associated with gram-negative sepsis and other infectious diseases, but the mechanisms by which they affect TLR4 signaling are unclear. In this study, we determined the impact of the D299G and T399I polymorphisms on TLR4 expression, interactions with myeloid differentiation factor 2 (MD2), LPS binding,...

Biglycan is a proteoglycan ubiquitously present in extracellular matrix of a variety of organs, including heart, and it was reported to be overexpressed in myocardial infarction. Myocardial infarction may be complicated by perimyocarditis through unknown mechanisms. Our aim was to investigate the capacity of TLR2/TLR4 ligand biglycan to enhance the presentation of specific Ags released upon car...

Background: This study characterized and compared the molecular profiles of CX3C chemokine receptor 1 (CX3CR1, a marker T-cell differentiation), Toll-like 4 (TLR4)-mediated interferon signaling pathway, immune checkpoints in different histological stages non-muscle invasive bladder cancer (NMIBC), aiming investigation these biomarkers as criterion clinical response to immunotherapy. Methods: Se...

A study by Cheng et al. in this issue of Science Signaling highlights the distinct single-cell signaling characteristics conferred by pathways mediated by the adaptor proteins MyD88 and TRIF in the TLR4-dependent activation of the transcription factor nuclear factor κB (NF-κB).

dsRNA is a common pathogen-associated molecular pattern that is recognized by cellular TLR3 and used by virus-infected cells to activate specific transcription factors and trigger induction of antiviral genes. In this article, we report a new branch of TLR3 signaling that does not lead to gene induction but affects many cellular properties, such as cell migration, adhesion, and proliferation. W...

OBJECTIVE Glatiramer acetate (GA; Copaxone), a disease-modifying therapy for multiple sclerosis (MS), promotes development of anti-inflammatory (M2, type II) monocytes that can direct differentiation of regulatory T cells. We investigated the innate immune signaling pathways that participate in GA-mediated M2 monocyte polarization. METHODS Monocytes were isolated from myeloid differentiation ...

In the course of the development of acquired immunodeficiency syndrome (AIDS), bacterial infection causes deleterious effects on the progression of the disease; bacterial LPS in the circulation activate immune cells, resulting in the acceleration of HIV replication. However, the precise HIV activation mechanisms in infected hosts remain largely unknown. Previously, we generated transgenic (Tg) ...

Hypoxia-ischemia is a common cause of neurological impairments in newborns, but little is known about how neuroinflammation contributes to the long-term outcome after a perinatal brain injury. In this study, we investigated the role of the fractalkine receptor chemokine CX3C motif receptor 1 (CX3CR1) and of toll-like receptor (TLR) signaling after a neonatal hypoxic-ischemic brain injury. Mice ...

TLR3 signaling is activated by dsRNA, a virus-associated molecular pattern. Injection of dsRNA into mice induced a rapid, dramatic, and reversible remodeling of the small intestinal mucosa with significant villus shortening. Villus shortening was preceded by increased caspase 3 and 8 activation and apoptosis of intestinal epithelial cells (IECs) located in the mid to upper villus with ensuing l...