Morphologic and immunohistochemical characterization of granulomas in the nucleotide oligomerization domain 2–related disorders Blau syndrome and Crohn disease

2012 ◽  
Vol 129 (4) ◽  
pp. 1076-1084 ◽  
Author(s):  
Carl E.I. Janssen ◽  
Carlos D. Rose ◽  
Gert De Hertogh ◽  
Tammy M. Martin ◽  
Brigitte Bader Meunier ◽  
...  
Keyword(s):  
Crohn Disease ◽  
Blau Syndrome ◽  
Nucleotide Oligomerization ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

Blau Arteritis Resembling Takayasu Disease with a Novel NOD2 Mutation

2012 ◽  
Vol 39 (9) ◽  
pp. 1888-1892 ◽  
Author(s):  
RAJU P. KHUBCHANDANI ◽  
RACHANA HASIJA ◽  
ISABELLE TOUITOU ◽  
CHETNA KHEMANI ◽  
CARINE H. WOUTERS ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Blau Syndrome ◽  
Current Case ◽  
Nod2 Mutation ◽  
Nucleotide Oligomerization ◽  
Exon 4 ◽  
Clinical Description ◽  
Takayasu Disease ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

Objective.To put forward a new concept — Blau arteritis, a form of large-vessel vasculitis phenotypically related to Takayasu disease but genetically and clinically part of an expanded phenotype of Blau syndrome.Methods.We provide a clinical description of a new case and summarize previously published cases of arteritis associated with Blau syndrome. Genetic testing was performed by direct sequencing of exon 4 of the NOD2 gene.Results.The case described and those reviewed from the literature demonstrate the emerging phenotype of Takayasu-like arteritis in patients with Blau syndrome. Although most patients described to date depict an otherwise classic Blau syndrome phenotype, the current case was atypical in that the predominant features were arteritic. A novel substitution, G464W, in a highly conserved position near the nucleotide oligomerization domain of the NOD2 protein is also described.Conclusion.Blau arteritis can be observed in the context of both typical and atypical (incomplete) Blau syndrome. The associated mutation in the NOD2 gene raises the question of the potential importance of this gene among patients with “primary” forms of Takayasu arteritis.

scholarly journals Stimulation of Nucleotide Oligomerization Domain and Toll-Like Receptors 2 to Enhance the Effect of Bacillus Calmette Guerin Immunization for Prevention of Mycobacterium Tuberculosis Infection: Protocol for a Series of Preclinical Randomized Controlled Trials (Preprint)

2018 ◽  
Author(s):  
Michael Eisenhut
Keyword(s):  
Innate Immunity ◽  
Mycobacterium Tuberculosis ◽  
Bacillus Calmette Guerin ◽  
Infection Rates ◽  
Ifn Gamma ◽  
Prevention Of Infection ◽  
Nucleotide Oligomerization ◽  
Stimulation Of ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

BACKGROUND Bacillus calmette guerin (BCG) immunization has been associated with a reduction in Mycobacterium tuberculosis (MTB) infection. BCG immunization has been shown to enhance innate immunity. This effect of BCG can be explained by an enhancing effect on innate immunity. OBJECTIVE This study aimed to test the following hypotheses: (1) BCG immunization can prevent infection with MTB, (2) prevention of infection occurs via stimulation of NOD2 (nucleotide oligomerization domain) and toll-like receptors 2 (TLR2), and (3) the effect of BCG immunization on prevention of infection with MTB can be enhanced by giving stimulators of NOD2 and TLR2. METHODS To detect the influence of immunization on infection rates, the ultralow dose (ULD) infection model is used. The infection rate of mice vaccinated with BCG and exposed after 6 weeks to ULD of MTB and unvaccinated mice are compared via cultures of lung homogenates and interferon (IFN) gamma release assay. If a reduced infection rate by BCG immunization is confirmed, the experiment is repeated by giving BCG combined simultaneously or in time sequence with the enhancers of innate immunity murabutide or beta-glycan. The influence of murabutide or beta-glycan alone on infection rates is investigated. To quantify the contribution of innate immunity levels of tumor necrosis factor, IFN gamma expression, histone H3 K4me3 trimethylation, and concentrations of monocytes with features of activation of innate immunity as defined by the Ly6Chigh as well as CD11b positive phenotype in immunized versus unimmunized infected and uninfected mice in the various immunization protocols is compared. The experiments will be repeated with prior application of the inhibitors of epigenetic programming of innate immunity histone methyltransferase inhibitor 5’-deoxy-5’-methylthio-adenosine and histone acetyl transferase inhibitor epigallocatechin-3-gallate. The influence of BCG on innate immunity is further corroborated by a prospective observational study in human infants. RESULTS Investigations of derivatives of muramyl dipeptide (MDP) to enhance early immunity in the C57BL/6 mouse strain (mice aged 7 weeks) by another group used 300 micrograms per mouse of oil-associated 6-0-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) 50/50 mixed with Freund’s incomplete adjuvant. Comparison of colony-forming unit (CFU) count in the lungs 3 weeks after aerosol challenge with Mycobacterium bovis of groups (n=5) between groups receiving mycol-MDP in oil emulsion (see above) versus controls (n=5) showed a significantly lower CFU count of 94.5 x106 (SD 22.0) in cases versus controls with 204.0 X 106 (SD 77.6). It is important to note that after elimination of T-cells in this model, a reduction of CFU in lungs of mice treated with mycol-MDP persisted albeit without statistical significance, which was possibly related to the small number of animals used. CONCLUSIONS Demonstration of a reduction of MTB infection by enhancement of innate immunity could show a new approach to improving vaccine efficacy against this pathogen. INTERNATIONAL REGISTERED REPOR PRR1-10.2196/13045

scholarly journals Nonhematopoietic Cells Control the Outcome of Infection with Listeria monocytogenes in a Nucleotide Oligomerization Domain 1-Dependent Manner

2009 ◽  
Vol 77 (7) ◽  
pp. 2908-2918 ◽  
Author(s):  
Ahmed Mosa ◽  
Christian Trumstedt ◽  
Emma Eriksson ◽  
Oliver Soehnlein ◽  
Frank Heuts ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Listeria Monocytogenes ◽  
Bacterial Load ◽  
Dependent Manner ◽  
Inflammatory Monocytes ◽  
Defensive Role ◽  
Nucleotide Oligomerization ◽  
Increased Susceptibility ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

ABSTRACT We analyzed the defensive role of the cytosolic innate recognition receptor nucleotide oligomerization domain 1 (NOD1) during infection with Listeria monocytogenes. Mice lacking NOD1 showed increased susceptibility to systemic intraperitoneal and intravenous infection with high or low doses of L. monocytogenes, as measured by the bacterial load and survival. NOD1 also controlled dissemination of L. monocytogenes into the brain. The increased susceptibility to reinfection of NOD1−/− mice was not associated with impaired triggering of listeria-specific T cells, and similar levels of costimulatory molecules or activation of dendritic cells was observed. Higher numbers of F480+ Gr1+ inflammatory monocytes and lower numbers of F480− Gr1+ neutrophils were recruited into the peritoneum of infected WT mice than into the peritoneum of infected NOD1−/− mice. We determined that nonhematopoietic cells accounted for NOD1-mediated resistance to L. monocytogenes in bone marrow radiation chimeras. The levels of NOD1 mRNA in fibroblasts and bone marrow-derived macrophages (BMM) were upregulated after infection with L. monocytogenes or stimulation with different Toll-like receptor ligands. NOD1−/− BMM, astrocytes, and fibroblasts all showed enhanced intracellular growth of L monocytogenes compared to WT controls. Gamma interferon-mediated nitric oxide production and inhibition of L. monocytogenes growth were hampered in NOD1−/− BMM. Thus, NOD1 confers nonhematopoietic cell-mediated resistance to infection with L. monocytogenes and controls intracellular bacterial growth in different cell populations in vitro.

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