scholarly journals Species-specific engagement of human nucleotide oligomerization domain 2 (NOD)2 and Toll-like receptor (TLR) signalling upon intracellular bacterial infection: role of Crohn's associated NOD2 gene variants

2015 ◽  
Vol 179 (3) ◽  
pp. 426-434 ◽  
Author(s):  
M. Salem ◽  
J. B. Seidelin ◽  
S. Eickhardt ◽  
M. Alhede ◽  
G. Rogler ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Gene Variants ◽  
Toll Like Receptor ◽  
Nucleotide Oligomerization ◽  
Species Specific ◽  
Tlr Signalling ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

Activation of nucleotide oligomerization domain containing protein 1 induces lipolysis through NF-κB and the lipolytic PKA activation in 3T3-L1 adipocytes

2013 ◽  
Vol 91 (6) ◽  
pp. 428-434 ◽  
Author(s):  
Jaanki S. Purohit ◽  
Pan Hu ◽  
Guoxun Chen ◽  
Jay Whelan ◽  
Naima Moustaid-Moussa ◽  
...  
Keyword(s):  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Camp Production ◽  
Nucleotide Oligomerization ◽  
Hormone Sensitive ◽  
Sirna Knockdown ◽  
Dose Dependent ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

Obesity is associated with chronic inflammation. Toll-like receptors (TLR) and NOD-like receptors (NLR) are two families of pattern recognition receptors that play important roles in the immune response and inflammation in adipocytes. Activation of TLR4 has been shown to stimulate lipolysis from adipose tissue or adipocytes. However, effects of activation of nucleotide-oligomerization domain containing protein 1 (NOD1), one of the prominent members of NLRs, on adipocyte lipolysis have not been studied. Here we report that NOD1 activation by the synthetic ligands (Tri-DAP and C12-iEDAP) stimulated lipolysis in 3T3-L1 adipocytes in a time- and dose-dependent manner. C12-iEDAP-induced lipolysis was attenuated with NOD1 siRNA knockdown, demonstrating the specificity of the effects. Moreover, inhibition of the protein kinase A (PKA)/hormone sensitive lipase (HSL) and NF-κB pathways by the pharmacological inhibitors attenuated the lipolytic effects of C12-iEDAP. Furthermore, we show NOD1 activation induced PKA activation independent of cAMP production and inhibition of NF-κB pathways attenuated phosphorylation of selected PKA lipolytic targets (phosphorylation of Perilipin Ser 517 and HSL Ser 563). Taken together, our results demonstrate a novel role of NOD1 activation, via NF-κB/PKA lipolytic activation, in inducing lipolysis in adipocytes and suggest that NOD1 activation may contribute to dyslipidemia in obesity.

scholarly journals Nucleotide Oligomerization Domain 2 (Nod2) Is Not Involved in the Pattern Recognition of Candida albicans

2006 ◽  
Vol 13 (3) ◽  
pp. 423-425 ◽  
Author(s):  
Chantal A. A. van der Graaf ◽  
Mihai G. Netea ◽  
Barbara Franke ◽  
Stephen E. Girardin ◽  
Jos W. M. van der Meer ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Candida Albicans ◽  
Cytokine Production ◽  
Nucleotide Binding ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Nucleotide Oligomerization ◽  
Toll Like Receptor 2 ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

ABSTRACT Nucleotide-binding oligomerization domain 2 (Nod2) pathways are known to interact with Toll-like receptor 2 (TLR2) and TLR4, which are pattern recognition receptors for Candida albicans. We observed that the prevalence of Nod2 polymorphisms was not increased in patients with Candida infections. Candida-induced cytokine production in individuals with Nod2 polymorphisms was unaffected. We conclude that Nod2 is unlikely to play an important role in the recognition of Candida albicans.

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

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