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NOD-like Receptors (nod-like + receptor)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity

ARTHRITIS & RHEUMATISM, Issue 2 2009
Tammy M. Martin
Objective Blau syndrome is a rare, autosomal-dominant, autoinflammatory disorder characterized by granulomatous arthritis, uveitis, and dermatitis. Genetics studies have shown that the disease is caused by single nonsynonymous substitutions in NOD-2, a member of the NOD-like receptor or NACHT,leucine-rich repeat (NLR) family of intracellular proteins. Several NLRs function in the innate immune system as sensors of pathogen components and participate in immune-mediated cellular responses via the caspase 1 inflammasome. Mutations in a gene related to NOD-2, NLRP3, are responsible for excess caspase 1,dependent interleukin-1, (IL-1,) in cryopyrinopathies such as Muckle-Wells syndrome. Furthermore, functional studies demonstrate that caspase 1,mediated release of IL-1, also involves NOD-2. The aim of this study was to test the hypothesis that IL-1, may mediate the inflammation seen in patients with Blau syndrome. Methods IL-1, release was measured in peripheral blood mononuclear cells cultured in vitro, obtained from 5 Blau syndrome individuals with a NOD2 (CARD15) mutation. Results We observed no evidence for increased IL-1, production in cells obtained from subjects with Blau syndrome compared with healthy control subjects. Furthermore, we presented 2 cases of Blau syndrome in which recombinant human IL-1 receptor antagonist (anakinra) was ineffective treatment. Conclusion Taken together, these data suggest that in contrast to related IL-1,,dependent autoinflammatory cryopyrinopathies, Blau syndrome is not mediated by excess IL-1, or other IL-1 activity. [source]

Harnessing human dendritic cell subsets for medicine

IMMUNOLOGICAL REVIEWS, Issue 1 2010
Hideki Ueno
Summary:, Immunity results from a complex interplay between the antigen-non-specific innate immune system and the antigen-specific adaptive immune system. The cells and molecules of the innate system employ non-clonal recognition receptors including lectins, Toll-like receptors, NOD-like receptors, and helicases. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing antigens or their derived peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). DCs can induce such contrasting states as immunity and tolerance. The recent years have brought a wealth of information on the biology of DCs revealing the complexity of this cell system. Indeed, DC plasticity and subsets are prominent determinants of the type and quality of elicited immune responses. In this article, we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines. [source]

Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors

JOURNAL OF INTERNAL MEDICINE, Issue 6 2007
B. Albiger
Abstract. The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs. [source]

Listeria monocytogenes infection in the face of innate immunity

CELLULAR MICROBIOLOGY, Issue 5 2009
Sinead C. Corr
Summary Pathogen recognition and induction of immune responses are important for efficient elimination of infection. However, pathogens such as Listeria monocytogenes employ strategies to evade or modulate these defences, thus creating a more favourable environment that ensures their survival and pathogenesis. New insights into these strategies, particularly those targeting innate immunity, have recently emerged. L. monocytogenes is initially detected at the cell surface or in phagosomes by toll-like receptor 2 and in the cytosol by nuclear oligodimerization domain (NOD)-like receptors (NOD1, NOD2) and NALP3 and Ipaf. It carries out N-deacetylation of peptidoglycan to avoid this detection by toll-like receptor 2 and NOD-like receptors. L. monocytogenes modulates transcription of host immunity genes through modification of histones and chromatin remodelling. Furthermore, L. monocytogenes has recently been shown to avoid autophagy and induce apoptosis in immune effector cells. In this review we discuss some of these strategies, which have provided new insights into the interaction between L. monocytogenes and the immune response at a crucial stage of infection. [source]

Signaling pathways in innate immunity

ACTA OPHTHALMOLOGICA, Issue 2008
A SALMINEN
Inflammation has a key role in the pathogenesis of AMD. This lecture will review the recent progress in understanding the different host-defence mechanisms against pathogens and self-based danger signals involved in the activation of innate immunity. The innate defence system utilizes pattern recognition receptors (PRR) to respond to a variety of pathogen-associated (PAMP) and danger-associated (DAMP) molecular structures. Along with the well-known complement and scavenger receptor systems, Toll-like receptors (TLR) and NOD-like receptors (NLR) have also a crucial part in host-defence and these receptor systems can be activated both by PAMPs and DAMPs. Pattern recognition receptors are located either in cell surface, such as TLR2 and TLR4, or in intracellular locations, e.g. TLR3, TLR9 and all NLRs. PRRs show some specificity to ligands and also in downstream they activate different signaling pathways, most common of which are NF-kB and IRF-dependent pathways inducing inflammatory responses. Retinal pigment epithelial cells (RPE) have an important role in eye host-defence, both at apical and basolateral surfaces. Most of the TLRs are expressed in RPE cells, especially TLR3 and TLR4, and they can participate in photoreceptor outer segment recognition. TLR3 can also suppress angiogenesis. The functions of NLRs, e.g. those forming inflammasomes, are still unknown, although the danger-type of activation signals, such as oxidative stress and potassium efflux, are present in retinal pigment epithelium. It seems that the activation of innate immunity system via DAMPs and PRRs may have a central role in the pathogenesis of AMD. [source]