Prevention of the enhancing effect of mucin and iron in mouse meningococcal infection

1983 ◽  
Vol 29 (12) ◽  
pp. 1671-1674 ◽  
Author(s):  
J. M. Dupuy ◽  
B. G. Sparkes ◽  
M. Desrosiers ◽  
E. Skamene ◽  
V. V. Micusan
Keyword(s):  
Listeria Monocytogenes ◽  
Neisseria Meningitidis ◽  
Crude Extract ◽  
Concomitant Administration ◽  
Reticuloendothelial System ◽  
Meningococcal Infection ◽  
Nonspecific Resistance ◽  
Enhancing Effect ◽  
Proteose Peptone

In vivo resistance of mice to Neisseria meningitidis was entirely abrogated by a concomitant administration of mucin and iron with N. meningitidis organisms. Resistance, however, was restored when the latter challenge was given to animals which had been immunized 7 days previously with a crude extract of meningococcal antigens (MA), BCG, or proteose peptone. These results suggest that depression or activation of the reticuloendothelial system (RES) may be important in resistant of mice to meningococcal infection. Also, like BCG, MA inoculation was able to prevent infection by Listeria monocytogenes indicating its marked ability to activate the RES. The data show that immunization can induce nonspecific RES stimulation and that the nonspecific resistance persists for at least 7 days.

scholarly journals Immune Homeostatic Macrophages Programmed by the Bacterial Surface Protein NhhA Potentiate Nasopharyngeal Carriage ofNeisseria meningitidis

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiao Wang ◽  
Mikael Sjölinder ◽  
Yumin Gao ◽  
Yi Wan ◽  
Hong Sjölinder
Keyword(s):  
Neisseria Meningitidis ◽  
Surface Protein ◽  
Meningococcal Infection ◽  
Necrosis Factor Alpha ◽  
Bacterial Surface ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory ◽  
Nasopharyngeal Mucosa

ABSTRACTNeisseria meningitidiscolonizes the nasopharyngeal mucosa of healthy populations asymptomatically, although the bacterial surface is rich in motifs that activate the host innate immunity. What determines the tolerant host response to this bacterium in asymptomatic carriers is poorly understood. We demonstrated that the conserved meningococcal surface protein NhhA orchestrates monocyte (Mo) differentiation specifically into macrophage-like cells with a CD200Rhiphenotype (NhhA-Mφ). In response to meningococcal stimulation, NhhA-Mφ failed to produce proinflammatory mediators. Instead, they upregulated interleukin-10 (IL-10) and Th2/regulatory T cell (Treg)-attracting chemokines, such as CCL17, CCL18, and CCL22. Moreover, NhhA-Mφ were highly efficient in eliminating bacteria. Thein vivovalidity of these findings was corroborated using a murine model challenged withN. meningitidissystematically or intranasally. The NhhA-modulated immune response protected mice from septic shock; Mo/Mφ depletion abolished this protective effect. Intranasal administration of NhhA induced an anti-inflammatory response, which was associated withN. meningitidispersistence at the nasopharynx.In vitrostudies demonstrated that NhhA-triggered Mo differentiation occurred upon engaged Toll-like receptor 1 (TLR1)/TLR2 signaling and extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) activation and required endogenously produced IL-10 and tumor necrosis factor alpha (TNF-α). Our findings reveal a strategy that might be adopted byN. meningitidisto maintain asymptomatic nasopharyngeal colonization.IMPORTANCENeisseria meningitidisis an opportunistic human-specific pathogen that colonizes the nasopharyngeal mucosa asymptomatically in approximately 10% of individuals. Very little is known about how this bacterium evades immune activation during the carriage stage. Here, we observed thatN. meningitidis, via the conserved surface protein NhhA, skewed monocyte differentiation into macrophages with a CD200Rhiphenotype. Bothin vivoandin vitrodata demonstrated that these macrophages, upon meningococcal infection, played an important role in forming a homeostatic immune microenvironment through their capacity to eliminate invading bacteria and to generate anti-inflammatory mediators. This work provides novel insight into the mechanisms underlying the commensal persistence ofN. meningitidis.

scholarly journals Molecular and Biological Analysis of Eight Genetic Islands That Distinguish Neisseria meningitidis from the Closely Related Pathogen Neisseria gonorrhoeae

2000 ◽  
Vol 68 (4) ◽  
pp. 2082-2095 ◽  
Author(s):  
Silke R. Klee ◽  
Xavier Nassif ◽  
Barica Kusecek ◽  
Petra Merker ◽  
Jean-Luc Beretti ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Neisseria Meningitidis ◽  
Dna Sequences ◽  
Subtractive Hybridization ◽  
Bactericidal Effect ◽  
Meningococcal Infection ◽  
Infant Rat ◽  
Disulfide Oxidoreductase

ABSTRACT The pathogenic species Neisseria meningitidis andNeisseria gonorrhoeae cause dramatically different diseases despite strong relatedness at the genetic and biochemical levels.N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. gonorrhoeae. We previously used subtractive hybridization to identify DNA sequences which might encode functions specific to bacteremia and invasion of the meninges because they are specific toN. meningitidis and absent from N. gonorrhoeae. In this report we show that these sequences mark eight genetic islands that range in size from 1.8 to 40 kb and whose chromosomal location is constant. Five of these genetic islands were conserved within a representative set of strains and/or carried genes with homologies to known virulence factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy identified one island, region 8, which is needed to induce bacteremia in an infant rat model of meningococcal infection. Region 8 encodes a putative siderophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neither were the mutant strains altered in their ability to interact with endothelial cells, suggesting that such interactions are not encoded by large genetic islands in N. meningitidis.

Accumulation of Macromolecular Particles in the Reticuloendothelial System (RES) Mediated by Platelet Aggregation and Disaggregation

1969 ◽  
Vol 22 (03) ◽  
pp. 496-507 ◽  
Author(s):  
W.G van Aken ◽  
J Vreeken
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Reticuloendothelial System ◽  
Caproic Acid ◽  
Carbon Particles ◽  
Carbon Clearance ◽  
Aggregation And Disaggregation ◽  
Platelet Aggregates

SummaryCarbon particles cause platelet aggregation in vitro and in vivo. Prior studies established that substances which modify thrombocyte aggregation also influence the rate at which carbon is cleared from the blood.This study was performed in order to elucidate the mechanism by which the carbon-platelet aggregates specifically accumulate in the RES.Activation of fibrinolysis by urokinase or streptokinase reduced the carbon clearance rate, probably due to generated fibrinogen degradation products (FDP). Isolated FDP decreased the carbon clearance and caused disaggregation of platelets and particles in vitro. Inhibition of fibrinolysis by epsilon-amino-caproic acid (EACA), initially accelerated the disappearance of carbon and caused particle accumulation outside the RES, predominantly in the lungs. It is supposed that platelet aggregation and locally activated fibrinolysis act together in the clearance of particles. In the normal situation the RES with its well known low fibrinolytic activity, becomes the receptor of the particles.

scholarly journals Ovarian Accumulation of Nanoemulsions: Impact of Mice Age and Particle Size

2021 ◽  
Vol 22 (15) ◽  
pp. 8283
Author(s):  
Eike Folker Busmann ◽  
Julia Kollan ◽  
Karsten Mäder ◽  
Henrike Lucas
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Reticuloendothelial System ◽  
Systematic Investigation ◽  
Measured Signal ◽  
Reproductive Aging ◽  
Sex Steroid Hormone ◽  
Adult Mice ◽  
Radiant Efficiency

Nanotechnology in the field of drug delivery comes with great benefits due to the unique physicochemical properties of newly developed nanocarriers. However, they may come as well with severe toxicological side effects because of unwanted accumulation in organs outside of their targeted site of actions. Several studies showed an unintended accumulation of various nanocarriers in female sex organs, especially in the ovaries. Some led to inflammation, fibrosis, or decreasing follicle numbers. However, none of these studies investigated ovarian accumulation in context to both reproductive aging and particle size. Besides the influences of particle size, the biodistribution profile may be altered as well by reproductive aging because of reduced capacities of the reticuloendothelial system (RES), changes in sex steroid hormone levels as well as altering ovarian stromal blood flow. This systematic investigation of the biodistribution of intravenously (i.v) injected nanoemulsions revealed significant dependencies on the two parameters particle size and age starting from juvenile prepubescent to senescent mice. Using fluorescent in vivo and ex vivo imaging, prepubescent mice showed nearly no accumulation of nanoemulsion in their uteri and ovaries, but high accumulations in the organs of the RES liver and spleen independently of the particle size. In fertile adult mice, the accumulation increased significantly in the ovaries with an increased particle size of the nanoemulsions by nearly doubling the portion of the average radiant efficiency (PARE) to ~10% of the total measured signal of all excised organs. With reproductive aging and hence loss of fertility in senescent mice, the accumulation decreased again to moderate levels, again independently of the particle size. In conclusion, the ovarian accumulation of these nanocarriers depended on both the age plus the particle size during maturity.

scholarly journals Asciminib Mitigates DNA Damage Stress Signaling Induced by Cyclophosphamide in the Ovary

2021 ◽  
Vol 22 (3) ◽  
pp. 1395
Author(s):  
Luca Mattiello ◽  
Giulia Pucci ◽  
Francesco Marchetti ◽  
Marc Diederich ◽  
Stefania Gonfloni
Keyword(s):  
Ovarian Reserve ◽  
Kinase Inhibitor ◽  
Concomitant Administration ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Abl Tyrosine Kinase ◽  
Negative Impacts ◽  
Abl Tyrosine Kinase Inhibitor

Cancer treatments can often adversely affect the quality of life of young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth. Herein, we demonstrate the in vivo protective effect of the allosteric Bcr-Abl tyrosine kinase inhibitor Asciminib on signaling pathways activated by cyclophosphamide in mouse ovaries. We also provide evidence that Asciminib does not interfere with the cytotoxic effect of cyclophosphamide in Michigan Cancer Foundation (MCF)7 breast cancer cells. Our data indicate that concomitant administration of Asciminib mitigates the cyclophosphamide-induced ovarian reserve loss without affecting the anticancer potential of cyclophosphamide. Taken together, these observations are relevant for the development of effective ferto-protective adjuvants to preserve the ovarian reserve from the damaging effects of cancer therapies.

scholarly journals Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

2005 ◽  
Vol 184 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Andrea C F Ferreira ◽  
Lívia P Lima ◽  
Renata L Araújo ◽  
Glaucia Müller ◽  
Renata P Rocha ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Iodine Content ◽  
Concomitant Administration ◽  
High Serum ◽  
Sodium Iodide Symporter ◽  
Physiological Control ◽  
Iodide Uptake ◽  
Thyroid Hormone Biosynthesis ◽  
Serum Tsh

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium–iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

scholarly journals MisR/MisS Two-Component Regulon in Neisseria meningitidis

2007 ◽  
Vol 76 (2) ◽  
pp. 704-716 ◽  
Author(s):  
Yih-Ling Tzeng ◽  
Charlene M. Kahler ◽  
Xinjian Zhang ◽  
David S. Stephens
Keyword(s):  
Neisseria Meningitidis ◽  
Target Genes ◽  
Inner Core ◽  
Consensus Sequence ◽  
Meningococcal Infection ◽  
Type I ◽  
Mobility Shift ◽  
Iron Assimilation ◽  
Wide Range ◽  
Two Component

ABSTRACT Two-component regulatory systems are involved in processes important for bacterial pathogenesis. Inactivation of the misR/misS system in Neisseria meningitidis results in the loss of phosphorylation of the lipooligosaccharide inner core and causes attenuation in a mouse model of meningococcal infection. One hundred seventeen (78 up-regulated and 39 down-regulated) potential regulatory targets of the MisR/MisS (MisR/S) system were identified by transcriptional profiling of the NMBmisR mutant and the parental wild-type meningococcal strain NMB. The regulatory effect was further confirmed in a subset of target genes by quantitative real-time PCR and β-galactosidase transcriptional fusion reporter assays. The MisR regulon includes genes encoding proteins necessary for protein folding in the bacterial cytoplasm and periplasm, transcriptional regulation, metabolism, iron assimilation, and type I protein transport. Mutation in the MisR/S system caused increased sensitivity to oxidative stress and also resulted in decreased susceptibility to complement-mediated killing by normal human serum. To identify the direct targets of MisR regulation, electrophoretic mobility shift assays were carried out using purified MisR-His6 protein. Among 22 genes examined, misR directly interacted with 14 promoter regions. Six promoters were further investigated by DNase I protection assays, and a MisR-binding consensus sequence was proposed. Thus, the direct regulatory targets of MisR and the minimal regulon of the meningococcal MisR/S two-component signal transduction system were characterized. These data indicate that the MisR/S system influences a wide range of biological functions in N. meningitidis either directly or via intermediate regulators.

scholarly journals Toxicity and teratogenicity evaluation of hydroethanolic extract of momordica charantia fruit using zebrafish (DANIO RERIO) embryos model

2019 ◽  
Vol 10 (SPL1) ◽  
Author(s):  
Noor Izati Abd Aziz ◽  
Vikneswari Perumal ◽  
Suganya Murugesu ◽  
Qamar Uddin Ahmed ◽  
Bisha Fathamah Uzir ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Crude Extract ◽  
Momordica Charantia ◽  
Spinal Curvature ◽  
Zebrafish Embryos ◽  
Chemical Toxicity ◽  
Active Constituent ◽  
Hydroethanolic Extract ◽  
Danio Rerio Embryos

 The use of zebrafish vertebrate model in vivo analysis of the drug toxicity and efficacy, chemical toxicity, and safety is increasing in recent researches. Momordica charantia Linn (Cucurbitaceae) has been traditionally claimed for its many protective roles. However, the development of toxicity effect may cause morphological abnormalities by using an embryo of zebrafish (Danio Rerio) is unknown. Hence, this study was designed to determine the toxicity and teratogenic effect of hydroethanolic extract of M. charantia fruit using Zebrafish (Danio Rerio) embryos. The crude extract was prepared from the fruit of M. charantia using 80% hydroethanolic solvent. The zebrafish embryos were exposed to serial dilution of crude extract. The active constituent was analyzed using gas chromatography coupled with mass spectrophotometry (GC-MS) Momordica charantia Linn (Cucurbitaceae) has been widely commercialized based on traditional usage as an antidiabetic product. The current study has shown the toxic effects of the M.  charantia fruit extract on the developing zebrafish embryos, and the median lethal concentration (LC50) was calculated to be 725.90 mg/L at 48 hpt. The observed effects are dependent on the time of exposure and concentrations of the extract. At higher concentration, the extract causes some morphological defects such as less pigmentation, dented tail, spinal curvature, oedema, reduced hatchability, and growth retardation, that indicates the presence of toxicant(s). Based on the GC-MS profiling, some of the compounds identified in the hydroethanolic extract, such as propanedioic acid and glutamine, may have caused the teratogenic effects to the embryos. Further research on the M. charantia fruit's metabolites should be carried out prior to any nutraceutical or pharmaceutical application.

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