Innate immune factors exert widespread effects on cytokine secretion, cell survival, autophagy, and apoptosis. Nucleotide-binding and oligomerization domain-like receptors (NLRs) are members of the innate immune system in the cytosol that sense pathogens, endogenous danger molecules such as uric acid, and pollutants. Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and...

We recently reported that induction of NOD2 by human Cytomegalovirus (HCMV) resulted in virus inhibition and upregulation of antiviral and inflammatory cytokines. Here we investigated the effects of muramyl dipeptide (MDP), a bacterial cell wall component that activates NOD2, on HCMV replication and antiviral responses. HCMV infection of human foreskin fibroblasts induced NOD2, the downstream r...

In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pedi...

BACKGROUND & AIMS The Cdcs1 locus of the C3Bir mouse confers severe colitis associated with a decrease in innate immune function and an increase in adaptive T-cell responses to commensal bacterial products. The aim of our study was to determine if defects in innate immunity are similarly associated with increased adaptive immune responses to microbial antigens in Crohn's disease patients. MET...

NOD2 variants have been identified to be a susceptibility factor for Crohn's disease. The NOD2 protein is an intracellular sensor of the bacterial wall product muramyl dipeptide (MDP) and activates the transcription factor NF-kappaB upon MDP-binding. NOD2 variants are associated with reduced NF-kappaB activation and reduced production of epithelial derived antibacterial peptides such as defensi...

Members of the Nod-like receptor (NLR) family recognize intracellular pathogens and recruit a variety of effector molecules, including pro-caspases and kinases, which in turn are implicated in cytokine processing and NF-kappaB activation.In order to elucidate the intricate network of NLR signaling, which is still fragmentary in molecular terms, we applied comprehensive yeast two-hybrid analysis...

Muramyl dipeptide (MDP) is a peptidoglycan moiety derived from commensal and pathogenic bacteria, and a ligand of its intracellular sensor NOD2. Mutations in NOD2 are highly associated with Crohn disease, which is characterized by dysregulated inflammation in the intestine. However, the mechanism linking abnormality of NOD2 signaling and inflammation has yet to be elucidated. Here we show that ...

NOD2 signalling can both positively and negatively regulate Tolllike receptor (TLR) responses. Previous studies have shown that lack of NOD2 signalling (in NOD2 knockout mice) leads to increased peptidoglycan induction of interleukin (IL)-12 via TLR2. Studies in this issue of Gut show that lack of NOD2 signalling (in patients with NOD2 mutations) leads to decreased CpG induction of tumour necro...

Background: Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like (NLRs) are innate, damage-associated molecular patterns (DAMP) sensors. Their expressions in human periodontal resident cells reactions toward irritations, such as hypoxia lipopolysaccharide (LPS), remain not well characterized. This cross-sectional study aimed to investigate characterize TLRs, NOD1/...