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Results for “Receptors, Pattern Recognition”

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PubMed2004

Crystal structure of the C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein Ialpha.

Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind, and in some cases hydrolyze, peptidoglycans (PGNs) on bacterial cell walls. These molecules, which are highly conserved from insects to mammals, participate in host defense against both Gram-positive and Gram-negative bacteria. We report the crystal structure of the C-terminal PGN-binding domain of human PGRP-Ialpha in two oligomeric states, monomer and dimer, to resolutions of 2.80 and 1.65 A, respectively. In contrast to PGRPs with PGN-lytic amidase activity, no zinc ion is present in the PGN-binding site of human PGRP-Ialpha. The structure reveals that PGRPs exhibit extensive topological variability in a large hydrophobic groove, located opposite the PGN-binding site, which may recognize host effector proteins or microbial ligands other than PGN. We also show that full-length PGRP-Ialpha comprises two tandem PGN-binding domains. These domains differ at most potential PGN-contacting positions, implying different fine specificities. Dimerization of PGRP-Ialpha, which occurs through three-dimensional domain swapping, is mediated by specific binding of sodium ions to a flexible hinge loop, stabilizing the conformation found in the dimer. We further demonstrate sodium-dependent dimerization of PGRP-Ialpha in solution, suggesting a possible mechanism for modulating PGRP activity through the formation of multivalent adducts.

Amino Acid Sequence↗

PubMed2005

NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2.

Production of inducible antimicrobial peptides offers a first and rapid defense response of epithelial cells against invading microbes. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide induced in various epithelia upon extracellular as well as intracellular bacterial challenge. Nucleotide-binding oligomerization domain protein 2 (NOD2/CARD15) is a cytosolic protein involved in intracellular recognition of microbes by sensing peptidoglycan fragments (e.g. muramyl dipeptide). We used luciferase as a reporter gene for a 2.3-kb hBD-2 promoter to test the hypothesis that NOD2 mediates the induction of hBD-2. Activation of NOD2 in NOD2-overexpressing human embryonic kidney 293 cells through its ligand muramyl dipeptide (MDP) induced hBD-2 expression. In contrast, overexpression of NOD2 containing the 3020insC frame-shift mutation, the most frequent NOD2 variant associated with Crohn disease, resulted in defective induction of hBD-2 through MDP. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-kappaB and AP-1 in the hBD-2 promoter are required for NOD2-mediated induction of hBD-2 through MDP. Moreover, the NF-kappaB inhibitor Helenalin as well as a super-repressor form of the NF-kappaB inhibitor IkappaB strongly inhibited NOD2-mediated hBD-2 promoter activation. Expression of NOD2 was detected in primary keratinocytes, and stimulation of these cells with MDP induced hBD-2 peptide release. In contrast, small interference RNA-mediated down-regulation of NOD2 expression in primary keratinocytes resulted in a defective induction of hBD-2 upon MDP treatment. Together, these data suggest that NOD2 serves as an intracellular pattern recognition receptor to enhance host defense by inducing the production of antimicrobial peptides such as hBD-2.

Anti-Infective Agents↗

PubMed2005

Passive and active components of neonatal innate immune defenses.

Innate immune defenses are crucial for survival in the first days and weeks of life. At birth, newborns are confronted with a vast array of potentially pathogenic microorganisms that were not encountered in utero. At this age, cellular components of the adaptive immune system are in a naive state and are slow to respond. Antibodies received from the dam are essential for defense, but represent a finite and dwindling resource. Innate components of the immune system detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and their products) by means of pattern-recognition receptors (PRRs). Soluble mediators of the innate system such as complement proteins, pentraxins, collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to structures on pathogens, leading to agglutination, interference with receptor binding, opsonization, neutralization, direct membrane damage and recruitment of additional soluble and cellular elements through inflammation. Cell-associated receptors such as the Toll-like receptors (TLRs) can activate cells and coordinate responses (both innate and adaptive). In this paper, accumulated knowledge of the receptors, soluble and cellular elements that contribute to innate defenses of young animals is reviewed. Research interest in this area has been intermittent, and the literature varies in quantity and quality. It is hoped that documentation of the limitations of our knowledge base will lead to more extensive and enlightening studies.

Animals↗

PubMed2001

Soluble CD14 in human breast milk and its role in innate immune responses.

Immune factors secreted in milk are important for health in the neonatal gut. We have detected the bacterial pattern recognition receptor, soluble CD14 (sCD14) in human breast milk at different times during lactation. The molecule occurs in a single form in milk, in contrast to human serum, in which there are two isoforms. Produced by mammary epithelial cells, milk sCD14 mediates secretion of innate immune response molecules such as interleukin-8, tumor necrosis factor-alpha, and epithelial neutrophil activator-78 by CD14-negative intestinal epithelial cells exposed to lipopolysaccharide (LPS) or bacteria. Although present at low concentrations in milk, LPS-binding protein may be implicated in the biological effects observed. Our findings support the premise that milk sCD14 acts as a 'sentinel' molecule and immune modulator in homeostasis and in the defense of the neonatal intestine. In so doing, it may prevent the immune and inflammatory conditions of the gut to which non-breastfed infants are predisposed.

Acute-Phase Proteins↗

PubMed2005

Aspergillus and asthma--any link?

The innate immune and acquired immune responses are not separate, parallel systems but form interdependent components of a single integrated immune response. This is nicely highlighted by an expanding database demonstrating that the innate immune response provides the acquired immune response with information about the origin of the antigen and the type of response required via pattern recognition receptors (PRRs). Aspergillus is among a growing list of allergens that can aggravate asthmatic responses. Significant pulmonary pathology is associated with Aspergillus-induced allergic and asthmatic lung disease characterized by increased Th2 cytokine generation, IgE and IgG, eosinophilia, airway hyper-responsiveness and airway remodeling. Experimental data from a model of chronic fungal asthma demonstrate that thymus associated and regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22), working via CCR4, directly impair the innate anti-fungal immune response, thereby promoting the maintenance of acquired Th2-mediated asthmatic disease. Both chemokines appear to accomplish this by regulating the expression of PRRs such as toll like receptors (TLRs) and triggering receptor expressed on myeloid cells (TREM-1) by immune cells. Thus, the link between Aspergillus and asthma appears to reside in the magnitude and appropriateness of the host innate immune response, and ongoing research is revealing promising targets for therapy.

Animals↗

PubMed2006

Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection.

To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1beta secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection.

Adaptor Proteins, Signal Transducing↗

PubMed2004

T cells from a high proportion of apparently naive cattle can be activated by modified vaccinia virus Ankara (MVA).

Modified vaccinia virus Ankara (MVA) was used as a vector to express genes from bovine respiratory syncytial virus (BRSV). Using these recombinant viruses as recall antigens for cells from BRSV-immuned cattle proved to be problematic because non-recombinant MVA itself frequently stimulated high levels of T lymphocyte activation. This phenomenon was observed in a high percentage of cattle from multiple herds. Gamma delta TCR(+) T cells were more sensitive to activation by MVA than other classes of T cells. A serological assay for MVA neutralization detected low, fluctuating titers of serum virus neutralizing (SVN) activity toward MVA in some cattle, but these were lower titers than those observed in cattle that underwent MVA vaccination. T cell reactivity in non-vaccinated cattle did not correlate significantly (p > 0.05) with SVN activity, undermining the notion that any adaptive immune response was responsible for the observed T cell sensitivity. More probable explanations are that MVA has mitogenic or superantigenic properties, or that the virus induces gammadelta TCR(+) T cell activation through interactions with innate pattern recognition receptors.

Animals↗

PubMed2001

From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA.

Several types of immune cells possess pattern recognition receptors (PRR) that can distinguish prokaryotic DNA from vertebrate DNA by detecting unmethylated CpG dinucleotides in particular base contexts (CpG motifs). Bacterial DNA or synthetic oligodeoxynucleotides containing these CpG motifs activate both innate and acquired immune responses that have evolved to protect against intracellular infections. These T helper 1 (Th1)-like immune responses include activation of B cells, dendritic cells, macrophages, and natural killer (NK) cells. CpG DNA-induced immune activation can protect against infection either alone or in combination with a vaccine and is effective in the immunotherapy of allergic diseases and cancer. Human clinical trials using such CpG DNA are currently underway.

Adjuvants, Immunologic↗

PubMed2006

Abeta-immunotherapy for Alzheimer's disease using mannan-amyloid-Beta peptide immunoconjugates.

In Alzheimer's disease (AD) the accumulation of pathological forms of the beta-amyloid (Abeta) peptide are believed to be causal factors in the neurodegeneration that results in the loss of cognitive function in patients. Anti-Abeta antibodies have been shown to reduce Abeta levels in transgenic mouse models of AD and in AN-1792 clinical trial on AD patients; however, the clinical trial was halted when some patients developed meningoencephalitis. Theories on the cause of the adverse events include proinflammatory "primed patients," a Th1-inducing adjuvant, and Abeta autoreactive T cells. New immunotherapy approaches are being developed to eliminate these putative risk factors. Mannan, which is recognized by pattern recognition receptors of the innate immune system, can be utilized as a molecular adjuvant to promote a Th2-mediated immune response to conjugated B cell epitopes. The N-terminus of Abeta was conjugated to mannan, and used to immunize mice with low concentrations of immunoconjugate, without a conventional adjuvant. Mannan induced a significant and highly polarized toward Th2 phenotype anti-Abeta antibody response not only in BALB/c, but also in B6SJL F1 mice. New preclinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse immune response that occurred in the first clinical trial.

Alzheimer Disease↗

PubMed2005

NOD1 variation, immunoglobulin E and asthma.

Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the gene. We found an insertion-deletion polymorphism (ND(1)+32656) near the beginning of intron IX that accounted for approximately 7% of the variation in IgE in two panels of families (P<0.0005 in each). Allele*2 (the insertion) was associated with high IgE levels. The same allele was strongly associated with asthma in an independent study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding of the two ND(1)+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND(1)+32656*1) was found to be associated with inflammatory bowel disease. The results indicate that intracellular recognition of specific bacterial products affects the presence of childhood asthma.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Chlamydia trachomatis-associated tubal factor subfertility: Immunogenetic aspects and serological screening.

Chlamydia (C.) trachomatis female genital tract infections usually remain asymptomatic and untreated. Therefore, an adequate immune response, rather than antibiotic treatment, is essential to clear the pathogen. Most women will effectively clear C. trachomatis infections, but some will have persistent C. trachomatis infections, which may ascend to the upper genital tract and increase the risk of tubal factor subfertility. Pattern recognition receptors (PRRs) of the toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD) families recognize C. trachomatis and initiate the immune response. Host immune factors are determinants of the course of C. trachomatis infections. Genetic variations in TLR and NOD genes may affect receptor function, leading to inadequate recognition of C. trachomatis, an inadequate immune response, and consequently an increased risk of persistence and late sequelae. For the risk assessment of tubal pathology in subfertile women, C. trachomatis immunoglobulin (Ig) G antibody testing (CAT) in serum is widely used. A positive CAT is indicative of a previous infection but not of a persistent infection. Measuring serological markers of persistence, of which C-reactive protein (CRP) seems promising, in CAT-positive women may identify a subgroup of subfertile women with persistent C. trachomatis infections and the highest risk of tubal pathology.

C-Reactive Protein↗

PubMed2003

Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent, NF-kappaB-independent pathway.

Recognition of bacterial products by the innate immune system is dependent on pattern-recognition receptors: toll-like receptor 9 (TLR-9) in the case of bacterial DNA. We hypothesized that bacterial DNA can directly affect enteric epithelial cells. RT-PCR revealed constitutive TLR-9 mRNA expression in three human colonic epithelial cell lines (T84, HT-29, Caco-2) and THP-1 monocytes. Epithelial cells, in six-well culture plates or on filter supports, were exposed to E. coli DNA (1-50 microg/ml), synthetic CpG-rich oligonucleotides, or calf thymus DNA for 6-48 h. Exposure to E. coli DNA resulted in an increase in IL-8 mRNA, and a time- and dose-dependent increase in IL-8 secretion. Also, CpG oligonucleotides induced epithelial IL-8 production, whereas calf thymus DNA did not. Exposure to E. coli DNA resulted in phosphorylation of ERK 1/2 MAPK and inhibitors of ERK activity (PD98059, UO126) significantly reduced the evoked IL-8 production. In contrast, inhibitors of NFkappaB activity (PDTC, SN50) did not block E. coli DNA-induced IL-8 production. Electrophoretic mobility shift assays revealed that E. coli DNA stimulated epithelial AP-1 but not NFkappaB activation. The barrier (i.e., transepithelial resistance) and ion transport parameters of epithelial monolayers (assessed in Ussing chambers) were unaltered following E. coli DNA exposure. Thus model gut epithelia express TLR-9 mRNA and, while maintaining their barrier function, can respond to E. coli DNA by increased IL-8 production.

Caco-2 Cells↗

PubMed2002

New perspectives on the immunology of chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis is a primary immune deficiency presenting as an inability to clear fungal infections and consequently as persisting and recurring infections of the skin and mucous membranes with yeasts, mostly Candida albicans. Chronic mucocutaneous candidiasis is a heterogeneous clinical syndrome which usually presents in childhood and can have an autosomal recessive, dominant or sporadic mode of inheritance. Most chronic mucocutaneous candidiasis patients also develop accompanying endocrine and inflammatory disorders that suggest an underlying deregulation of the immune system. It has long been recognized that protection from mucocutaneous candidiasis relies on cell-mediated immunity and studies on animal models have highlighted the essential role of type 1 cytokines in protection against Candida spp. Recent data in patients with chronic mucocutaneous candidiasis have documented altered patterns of cytokine production in response to Candida spp. with decreased production of some but not all type 1 cytokines and increased levels of interleukin-10. The defect underlying altered cytokine production remains unknown but studies are in progress addressing the putative role of dendritic cells and pattern recognition receptors in directing cytokine responses. These novel insights into immune mechanisms responsible for protection against Candida spp. are opening new possibilities of immunomodulation and vaccination that could prove beneficial in the management of chronic mucocutaneous candidiasis.

Adjuvants, Immunologic↗

PubMed2003

Association of the -159 C --> T polymorphism in the CD14 promoter with variations in serum lipoproteins in healthy subjects.

The CD14-159 C --> T polymorphism, a single nucleotide polymorphism (SNP) at position -159 in the promoter region of the gene encoding the pattern recognition receptor CD14, has been associated with elevated plasma concentrations of soluble CD14, lowered serum immunoglobulin E, increased risk for myocardial infarction, and decreased risk for allergy and asthma. In the present study, the CD14-159 C --> T polymorphism has been investigated in order to determine its frequency and association with proinflammatory variables and lipid profile traits of 117 volunteers. The frequency of the CD14 promoter genotype as determined by polymerase chain reaction amplification-restriction fragment length polymorphism analysis was 35.0% (CC), 44.4% (CT), and 20.5% (TT), and the T allele frequency was 42.7%. Compared with the other genotypes, notably CC homozygotes, TT homozygotes were associated with lower total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B-100 (P < 0.01) concentrations in serum. However, no association was found between the investigated SNP and inflammatory mediators such as fibrinogen, interleukin-6, tumor necrosis factor-alpha, tissue factor, C-reactive protein, plasminogen activator inhibitor-1, leukotriene B4, or thromboxane B2. In conclusion, the CD14-159 C --> T polymorphism may be an important genetic trait, related to the ability of CD14 to bind and transport lipids, such as cholesterol.

Adult↗

PubMed2003

Role of intestinal flora in the development of allergy.

PURPOSE OF REVIEW: The frequency of allergic diseases is increasing worldwide. Experimental and clinical studies have linked a reduced number of early infections to this trend. The gastrointestinal system, which comprises the largest lymphoid tissue and microbial reservoir of the body, has received more attention during the last few years as a potential determiner in the development of atopic disease. RECENT FINDINGS: Alterations in intestinal microbiota have been detected both in infants suffering from allergic disease and in those later developing the disorder. Delay in the compositional development of and in gut microflora was a general finding in allergic children. In a subsequent study, perinatal administration of lactobacilli halved the later development of atopic eczema during the first 2 years of life. Specific strains of the healthy gut microbiota have been shown to induce the production of IL-10 and transforming growth factor-beta, which possess an important regulative role in the development of allergic type immune response. Probiotics also strengthen gut defence barrier mechanisms and reduce antigen load in the gut. Pattern recognition receptors in intestinal epithelial and antigen-presenting cells have been demonstrated to mediate a continuing dialogue between host and gut microbiota. SUMMARY: Despite several promising findings, the exact role of gut normal microbiota in the development of allergy remains to be elucidated. For successful interventions, more data concerning a communication between host and specific microbial species are needed.

Animals↗

PubMed2006

Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes influence the risk for severe acute graft-versus-host disease in patients who underwent an allogeneic transplantation.

BACKGROUND: NOD2 and TLR-4 genes belong to the innate immune system that detects invading pathogens through several pattern-recognition receptors. Here we analyzed 403 patients for NOD2 gene mutations and 307 patients for TLR-4 gene mutations (Thr399Ile) with their respective donors and correlated the results with the incidence of acute graft-versus-host disease (aGVHD), severe acute GVHD (saGVHD), the risk for transplant-related mortality (TRM), overall survival (OS) and incidence of infectious complications. METHODS: We performed a retrospective single-center study. Genotyping of TLR-4 and NOD2 were evaluated by real-time polymerase chain reaction. RESULTS: Surprisingly, we found a significant reduced incidence of aGVHD, saGVHD, and intestinal GVHD for patients with NOD2 gene mutations on the donor side with 50%, 0% and 2% compared to patients with the wild-type NOD2 gene with 65%, 17%, and 26%, respectively (P<0.02). However, the incidence of saGVHD increased in patients with NOD2 mutations on the patient and donor (P/D) side with 44% versus 17% compared to patients with the wild-type gene (P<0.03). TLR-4 gene mutations at P/D side had an increased risk for saGVHD with 42% versus 15% of patients with wild-type gene (P<0.04). OS, TRM, and incidence of infectious complications were not influenced by the mutated genes. Multivariate analysis confirmed that NOD2 gene mutations on the donor side had a reduced risk for saGVHD (P<0.001), whereas mutations of the NOD2 gene on P/D side had an increased risk for saGVHD (P<0.01) in our analysis. CONCLUSIONS: These results suggest that NOD2 mutations have influence on the occurrence of acute GVHD after transplantation.

Acute Disease↗

PubMed2025

Exploring prognostic genes in the immune microenvironment of acute myeloid leukemia via weighted gene co-expression network analysis.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous blood cancer that arises from transformed myeloid precursor cells in a compromised bone marrow microenvironment. This environment is essential for AML initiation, progression, and relapse. Alongside oncogenic changes in hematopoietic cells, immunological dysregulation also contributes to leukemogenesis. The present study is aimed to identify prognostic genes in stromal and immune cells associated with AML using the weighted gene co-expression network analysis (WGCNA). METHODS: Gene expression profiles were retrieved from The Cancer Genome Atlas database, and immune and stromal cell scores were calculated using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) method. These scores helped identify differentially expressed genes (DEGs), which were then used to create gene clusters through WGCNA. To explore the functions of genes linked to AML subtypes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. A protein-protein interaction network was developed to identify hub genes. The top 18 hub genes were identified using the cytoHubba plug-in in Cytoscape software, and survival analysis was conducted with the Gene Expression Profiling Interactive Analysis 2 online tool. RESULTS: A total of 1097 DEGs were identified, with 601 being upregulated and 496 downregulated. WGCNA analysis indicated that the gray module, comprising 165 genes, had the strongest association with AML subtypes (Cor > 0.3; P < .05). Gene Ontology enrichment analysis demonstrated that the 18 identified hub genes were predominantly associated with neutrophil activation, immune response, secretory granule membrane, and pattern recognition receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were mainly involved in pathways related to phagosome, lysosome, tuberculosis, leishmaniasis, and neutrophil extracellular trap formation. Kaplan-Meier survival analysis of the top 18 hub genes indicated that ITGAM, IL10, and CD163 were significantly correlated with survival outcomes in AML. CONCLUSION: Key stromal and immune-related genes influencing AML patient outcomes were identified, highlighting their potential as therapeutic targets. These discoveries provide deeper insights into the molecular mechanisms driving AML pathogenesis and subtype differentiation.

Leukemia, Myeloid, Acute↗

PubMed2007

The role of altered microbial signaling via mutant NODs in intestinal inflammation.

PURPOSE OF REVIEW: Recently, a new class of intracellular pattern recognition receptors belonging to the family of nucleotide binding and oligomerization domain (NOD)-like receptors that includes NOD1, NOD2 and IPAF has been described. These proteins are involved in recognizing bacterial components or their degradation constituents that are delivered within the cytoplasm. In this review we will analyze the role of NOD proteins in regulating immune homeostasis. RECENT FINDINGS: After an initial description of advances in our understanding of the function of these proteins, this review will focus on the contradictory finding that even though mutations in NOD2 proteins lead to a loss of function phenotype, the outcome is an increased inflammatory response. Different hypotheses to reconcile this observation will be proposed. SUMMARY: The cellular and tissue distribution of NOD molecules as well as their role in regulating inflammatory cytokine release renders these proteins particularly important in controlling the development of inflammatory reactions. This is confirmed by the discovery that mutations in the genes that code for NOD1 and NOD2 confer increased susceptibility to inflammatory bowel disease. We will discuss NOD2 involvement in the development of Crohn's disease.

Animals↗