Abstract
Toll-like receptors (TLRs) recognize common motifs, pathogen-associated molecular patterns (PAMPs), in microorganisms. Bacterial PAMPs are mainly distributed on cell-surfaces. Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls. Muramyldipeptide (MDP; N-acetylmuramyl-L-alanyl-D-isoglutamine) is a common and key structure of PGNs and exhibits most the of bioactivities of PGNs. Recently, the intracellular receptor for MDP was revealed to be NOD2. Another bioactive moiety of PGNs, diaminopimelic acid (DAP) containing desmuramylpeptides (DMPs), senses another intracellular receptor, NOD1. MDP-primed mice exhibited hyper-responses to endotoxin and other bacterial components, which sense Toll-like receptors (TLRs), although MDP itself does not exhibit apparent activity in mice. On the other hand, DMPs exhibited definite activity in mice, and the most powerful DMP, FK565, exhibited stronger priming activity than MDP. In human monocytic cells, both MDP and DMPs exhibited definite activities; marked synergistic interleukin (IL)-8 secretion was induced by DMPs and MDP in combination with synthetic TLR agonists, and suppression of the mRNA expressions of NOD1 and NOD2, respectively, by RNA interference specifically inhibited synergistic IL-8 secretion. In human dendritic cells (DCs), synergistic T helper type 1 responses are induced by combined stimulations of synthetic NOD and TLR agonists. Considering these findings altogether, in host-bacteria interactions, host cells should recognize bacteria via both TLRs and NODs, which might induce synergistic innate and adaptive immune responses.
Keywords: peptidoglycans, muramyldipeptide, desmuramylpeptide, diaminopimelic acid, NOD1, NOD2, Toll-like receptors, LPS
Current Pharmaceutical Design
Title: Enhancement of TLR-Mediated Innate Immune Responses by Peptidoglycans through NOD Signaling
Volume: 12 Issue: 32
Author(s): H. Takada and A. Uehara
Affiliation:
Keywords: peptidoglycans, muramyldipeptide, desmuramylpeptide, diaminopimelic acid, NOD1, NOD2, Toll-like receptors, LPS
Abstract: Toll-like receptors (TLRs) recognize common motifs, pathogen-associated molecular patterns (PAMPs), in microorganisms. Bacterial PAMPs are mainly distributed on cell-surfaces. Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls. Muramyldipeptide (MDP; N-acetylmuramyl-L-alanyl-D-isoglutamine) is a common and key structure of PGNs and exhibits most the of bioactivities of PGNs. Recently, the intracellular receptor for MDP was revealed to be NOD2. Another bioactive moiety of PGNs, diaminopimelic acid (DAP) containing desmuramylpeptides (DMPs), senses another intracellular receptor, NOD1. MDP-primed mice exhibited hyper-responses to endotoxin and other bacterial components, which sense Toll-like receptors (TLRs), although MDP itself does not exhibit apparent activity in mice. On the other hand, DMPs exhibited definite activity in mice, and the most powerful DMP, FK565, exhibited stronger priming activity than MDP. In human monocytic cells, both MDP and DMPs exhibited definite activities; marked synergistic interleukin (IL)-8 secretion was induced by DMPs and MDP in combination with synthetic TLR agonists, and suppression of the mRNA expressions of NOD1 and NOD2, respectively, by RNA interference specifically inhibited synergistic IL-8 secretion. In human dendritic cells (DCs), synergistic T helper type 1 responses are induced by combined stimulations of synthetic NOD and TLR agonists. Considering these findings altogether, in host-bacteria interactions, host cells should recognize bacteria via both TLRs and NODs, which might induce synergistic innate and adaptive immune responses.
Export Options
About this article
Cite this article as:
Takada H. and Uehara A., Enhancement of TLR-Mediated Innate Immune Responses by Peptidoglycans through NOD Signaling, Current Pharmaceutical Design 2006; 12 (32) . https://dx.doi.org/10.2174/138161206778743510
DOI https://dx.doi.org/10.2174/138161206778743510 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Systematic Review on the Role of Arachidonic Acid Pathway in Multiple
Sclerosis
CNS & Neurological Disorders - Drug Targets Recent advances in the management of autoimmune myocarditis: insights from animal studies.
Current Pharmaceutical Design Radiolabeled Compounds in Diagnosis of Infectious and Inflammatory Disease
Current Pharmaceutical Design Sirolimus and its Analogs and its Effects on Vascular Diseases
Current Pharmaceutical Design Actively Targeted Nanoparticles for Drug Delivery to Tumor
Current Drug Metabolism Borna Disease Virus (BDV): Neuropharmacological Effects of a CNS Viral Infection
Current Neuropharmacology Pharmacological Targeting of IDO-Mediated Tolerance for Treating Autoimmune Disease
Current Drug Metabolism Dendritic Cell Endothelium Interaction in Autoimmunity
Current Pharmaceutical Design Oral Contraceptives and Autoimmune Diseases
Current Women`s Health Reviews A Translational View of Peptide Treatment of Neurological Disorders
Current Medicinal Chemistry CD26/Dipeptidyl Peptidase IV as a Novel Therapeutic Target for Cancer and Immune Disorders
Mini-Reviews in Medicinal Chemistry How to Get from Here to There: Macrophage Recruitment in Alzheimers Disease
Current Alzheimer Research Targeted Delivery of Montelukast for the Treatment of Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets From the Oxygen to the Organ Protection: Erythropoietin as Protagonist in Internal Medicine
Cardiovascular & Hematological Agents in Medicinal Chemistry The Anti-inflammatory Potential of Selected Plant-derived Compounds in Respiratory Diseases
Current Pharmaceutical Design Recent Applications of Birch Reduction in Total Synthesis of Natural Products
Current Organic Chemistry In vitro And In vivo Immunomodulating Properties of Mesenchymal Stem Cells
Recent Patents on Inflammation & Allergy Drug Discovery A Possible Role for Interleukin 37 in the Pathogenesis of Behcet's Disease
Current Molecular Medicine Biology of Mesenchymal Stem Cells
Current Rheumatology Reviews Dichotomous Life of DNA Binding High Mobility Group Box1 Protein in Human Health and Disease
Current Protein & Peptide Science