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Toxins Jul 2023On 6 July 2018, the Center for Epidemiology and Public Health of the French Armed Forces was informed of an outbreak of acute gastroenteritis among customers of a dining...
On 6 July 2018, the Center for Epidemiology and Public Health of the French Armed Forces was informed of an outbreak of acute gastroenteritis among customers of a dining facility at a military base in Brittany, France. A total of 200 patients were reported out of a population of 1700 (attack rate: 12%). The symptoms were mainly lower digestive tract disorders and occurred rapidly after lunch on 5 July (median incubation period: 3.3 h), suggesting a toxin-like pathogenic process. A case-control survey was carried out (92 cases and 113 controls). Statistical analysis pointed to the chili con carne served at lunch on 5 July as the very likely source of poisoning. Phytohaemagglutinin, a plant lectin, was found in the chili con carne at a concentration above the potentially toxic dose (400 HAU/gram). The raw kidney beans incorporated in the chili con carne presented a high haemagglutination activity (66,667 HAU/gram). They were undercooked, and the phytohaemagglutinin was not completely destroyed. FBDOs due to PHA are poorly documented. This study highlights the need to develop methods for routine testing of plant toxins in food matrices. Improved diagnostic capabilities would likely lead to better documentation, epidemiology, and prevention of food-borne illnesses caused by plant toxins.
Topics: Humans; Foodborne Diseases; Gastroenteritis; Toxins, Biological; Disease Outbreaks; Meat; France
PubMed: 37505726
DOI: 10.3390/toxins15070457 -
European Journal of Medicinal Chemistry Nov 2023Voltage-gated potassium channel K1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca...
Voltage-gated potassium channel K1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca homeostasis. Here, we present the structure-activity relationship, K1.3 inhibition, and immunosuppressive effects of new thiophene-based K1.3 inhibitors with nanomolar potency on K current in T-lymphocytes and K1.3 inhibition on Ltk cells. The new K1.3 inhibitor trans-18 inhibited K1.3 -mediated current in phytohemagglutinin (PHA)-activated T-lymphocytes with an IC value of 26.1 nM and in mammalian Ltk cells with an IC value of 230 nM. The K1.3 inhibitor trans-18 also had nanomolar potency against K1.3 in Xenopus laevis oocytes (IC = 136 nM). The novel thiophene-based K1.3 inhibitors impaired intracellular Ca signaling as well as T-cell activation, proliferation, and colony formation.
Topics: Animals; Mammals; Potassium Channel Blockers; Potassium Channels; Potassium Channels, Voltage-Gated; Structure-Activity Relationship; T-Lymphocytes; Thiophenes; Immunosuppressive Agents
PubMed: 37454520
DOI: 10.1016/j.ejmech.2023.115561 -
Journal of Physiology and Pharmacology... Apr 2023Some studies have shown that electromagnetic fields (EMFs) may impact immune response cells and their functions. The first stage of the defense from pathogens is innate...
Some studies have shown that electromagnetic fields (EMFs) may impact immune response cells and their functions. The first stage of the defense from pathogens is innate immunity encompassing phagocytosis and phagocytosis-related intracellular effects. Our work aimed to determine the influence of a low-frequency electromagnetic field (7 Hz, 30 mT) on the phagocytosis process of latex beads (LBs), the production of reactive oxygen species (ROS), and viability changes in a human monocytic Mono Mac 6 (MM6) cell line as an experimental model of the phagocytosing cells in in vitro cell culture conditions. For these purposes, cells were firstly activated with infectious agents such as lipopolysaccharide (LPS), Staphylococcal enterotoxin B (SEB), or the proliferatory agent phytohaemagglutinin (PHA), and then a phagocytosis test was performed. Cell viability and range of phagocytosis of latex beads by MM6 cells were measured by flow cytometry, and the level of ROS was evaluated with the use of a cytochrome C reduction test. The obtained results revealed that applied EMF exposure mainly increased the necrosis parameter of cell death when they were pre-stimulated with SEB as an infectious factor and subsequently phagocytosed LBs (P=0.001). Prestimulation with other agents like LPS or PHA preceding phagocytosis resulted in no statistically significant changes in cell death parameters. The level of ROS depended on the used stimulatory agent, phagocytosis, and/or EMF exposure. The obtained effects for EMF exposure indicated only a slight decrease in the ROS level for cells phagocytosing latex beads and being treated with SEB or PHA, while the opposite effect was observed for LPS pre-stimulated cells (data not statistically significant). The results concerning the viability of phagocytosing cells, the effectiveness of the phagocytosis process, and the level of radical forms might result from applied EMF parameters like signal waveform, frequency, flux density, and especially single EMF exposure.
Topics: Humans; Reactive Oxygen Species; Electromagnetic Fields; Microspheres; Lipopolysaccharides; Phagocytosis; Cell Line
PubMed: 37453098
DOI: 10.26402/jpp.2023.2.10 -
International Journal of Molecular... May 2023Aberrant expression of glycans, i.e., oligosaccharide moiety covalently attached to proteins or lipids, is characteristic of various cancers, including urothelial ones....
Aberrant expression of glycans, i.e., oligosaccharide moiety covalently attached to proteins or lipids, is characteristic of various cancers, including urothelial ones. The binding of lectins to glycans is classified as molecular recognition, which makes lectins a strong tool for understanding their role in developing diseases. Here, we present a quantitative approach to tracing glycan-lectin interactions in cells, from the initial to the steady phase of adhesion. The cell adhesion was measured between urothelial cell lines (non-malignant HCV29 and carcinoma HT1376 and T24 cells) and lectin-coated surfaces. Depending on the timescale, single-cell force spectroscopy, and adhesion assays conducted in static and flow conditions were applied. The obtained results reveal that the adhesion of urothelial cells to two specific lectins, i.e., phytohemagglutinin-L and wheat germ agglutinin, was specific and selective. Thus, these lectins can be applied to selectively capture, identify, and differentiate between cancer types in a label-free manner. These results open up the possibility of designing lectin-based biosensors for diagnostic or prognostic purposes and developing strategies for drug delivery that could target cancer-associated glycans.
Topics: Humans; Lectins; Urinary Bladder Neoplasms; Phytohemagglutinins; Wheat Germ Agglutinins; Polysaccharides
PubMed: 37175920
DOI: 10.3390/ijms24098213 -
International Journal of Molecular... Apr 2023Oedema disease (OD) in piglets is one of the most important pathologies, as it causes significant losses due to the high mortality because of the Shiga toxin family,...
Oedema disease (OD) in piglets is one of the most important pathologies, as it causes significant losses due to the high mortality because of the Shiga toxin family, which produces (STEC) strains. The main toxin responsible for the characteristic pathologies in pigs is Shiga toxin 2 subtype e (Stx2e). Moreover, there is growing evidence that Stx's family of toxins also targets immune cells. Therefore, this study evaluated the effect of different concentrations of Stx2e on porcine immune cells. Porcine peripheral blood mononuclear cells were pre-incubated with Stx2e, at three different concentrations (final concentrations of 10, 500, and 5000 CD50/mL) and with a negative control group. Cells were then stimulated with polyclonal mitogens: concanavalin A, phytohemagglutinin, pokeweed mitogen, or lipopolysaccharides. Cell proliferation was assessed by BrdU (or EdU) incorporation into newly created DNA. The activation of the lymphocyte subsets was assessed by the detection of CD25, using flow cytometry. The toxin significantly decreased mitogen-driven proliferation activity, and the effect was partially dose-dependent, with a significant impact on both T and B populations. The percentage of CD25+ cells was slightly lower in the presence of Stx2e in all the defined T cell subpopulations (CD4+, CD8+, and γδTCR+)-in a dose-dependent manner. B cells seemed to be the most affected populations. The negative effects of different concentrations of Stx2e on the immune cells in this study may explain the negative impact of the subclinical course of OD.
Topics: Swine; Animals; Shiga Toxin; Leukocytes, Mononuclear; Escherichia coli; Shiga Toxin 2; Escherichia coli Infections; Lymphocyte Subsets
PubMed: 37175714
DOI: 10.3390/ijms24098009 -
Frontiers in Immunology 2023Immune function in pregnancy is influenced by host-specific and environmental factors. This may impact fetal immune development, but the link between maternal and...
INTRODUCTION
Immune function in pregnancy is influenced by host-specific and environmental factors. This may impact fetal immune development, but the link between maternal and neonatal immune function is still poorly characterized. Here, we investigate the relationship between maternal and neonatal immune function, and identify factors affecting the association between maternal and child cytokine secretion.
METHODS
In the French prospective cohort SEPAGES, blood samples were obtained from pregnant women (n=322) at gestational week 20 ± 4 and from their child at birth (n=156). Maternal and cord blood cytokine and chemokine (CK) levels were measured at baseline in all subjects and after T cell or dendritic cell activation with phytohemagglutinin or R848 (in total 29 and 27 measures in maternal and cord blood samples, respectively). Associations between environmental, individual factors and CK level were estimated by linear regression modeling. The maternal-cord blood CK relations were assessed by Pearson correlation and regression models.
RESULTS
We observed that pregnant women and neonates displayed specific CK secretion profiles in the innate and adaptive compartments at baseline and upon activation. Activation of T cells in cord blood induced high levels of IL-2, but low levels of IFNγ, IL-13 or IL-10, in comparison to maternal blood samples. Elsewhere, neonatal innate immune responses were characterized by low production of IFNα, while productions of IL-1β, IL-6, IL-8, IL-10 and TNFα were higher than maternal responses. Strong correlations were observed between most CK after activation in maternal and cord blood samples. Strikingly, a statistical association between global mother and child cytokine profiles was evidenced. Correlations were observed between some individual CK of pregnant women and their children, both at baseline (MCP1, RANTES) and after activation with R848 (IL-6, IL-8 and IL-10). We looked for factors which could influence cytokine secretion in maternal or cord blood, and found that leucocyte counts, maternal age, pre-conception BMI, smoking and season were associated with the levels of several CK in mothers or children.
DISCUSSION
Our study reveals immune imprinting influencing immune responses in infants, opening the way to investigate the mechanisms responsible for this imprinting. Whether such influences have long lasting effects on children health warrants further investigation.
Topics: Infant, Newborn; Infant; Humans; Female; Pregnancy; Interleukin-10; Interleukin-8; Interleukin-6; Prospective Studies; Cytokines; Immunity, Innate; Mother-Child Relations
PubMed: 37081891
DOI: 10.3389/fimmu.2023.1136749 -
Pediatric Nephrology (Berlin, Germany) Dec 2023The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However,... (Review)
Review
The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised.
Topics: Child; Humans; Immunosuppressive Agents; Vaccines, Attenuated; Prospective Studies; Immune System Diseases; Communicable Diseases
PubMed: 37076756
DOI: 10.1007/s00467-023-05969-z -
Analytica Chimica Acta May 2023In this study, glycidyl methacrylate (GMA)-based materials functionalized with different galactose derivatives were prepared to be used as affinity sorbents for...
In this study, glycidyl methacrylate (GMA)-based materials functionalized with different galactose derivatives were prepared to be used as affinity sorbents for solid-phase extraction (SPE) of several food allergen lectins (such as phytohemagglutinin (PHA)). First, GMA-based polymers were synthesized and then galactose derivatives were immobilized onto the GMA surface using two different synthetic routes. In the first approach, the bare polymer was modified with ethylenediamine and glutaraldehyde, and subsequently two galactose derivatives were immobilized. In the second strategy, the starting polymer was modified with cystamine and gold nanoparticles (AuNPs), on which a thiolated galactose derivative was subsequently anchored. The resulting materials were characterized by scanning electron microscopy and used as SPE sorbents for the isolation of PHA (as probe protein) from food matrices. Different SPE parameters (sample pH, eluent solution composition, binding capacity, sample volume, selectivity and reusability) were evaluated. The material that provided the best PHA recovery (98%) was the one obtained in the second approach, being this material successfully applied to the selective extraction of PHA and other similar lectins from different foods (red and lima dried beans, fresh soybeans and biscuits containing soybean protein traces as indicated in their label). After SDS-PAGE of eluates, all samples only exhibited the characteristic PHA band around 30 kDa, suggesting the high potential of the developed material for application in food allergy field.
Topics: Humans; Polymers; Gold; Galactose; Lectins; Metal Nanoparticles; Methacrylates; Solid Phase Extraction; Food Hypersensitivity; Allergens
PubMed: 37032057
DOI: 10.1016/j.aca.2023.341142 -
Anais Da Academia Brasileira de Ciencias 2023Body temperature has relevant effects on the immune response. Here, we characterized the thermal biology and health condition of the viviparous lizard Liolaemus kingii...
Body temperature has relevant effects on the immune response. Here, we characterized the thermal biology and health condition of the viviparous lizard Liolaemus kingii from Patagonia (Argentina), by studying field body temperatures, presence of injuries or ectoparasites, body condition (BC), and individual immune response capacity with the phytohemagglutinin (PHA) skin-swelling assay. In addition, we analyzed the effects of injections of a bacterial endotoxin (lipopolysaccharide; LPS) on the preferred temperature (Tp) and BC of adult males and newborns. The PHA treatment caused detectable thickening at 2 and 20 hours post-assay in males, indicating a significant immune response related to an increase in cellular activity. LPS-challenged lizards thermoregulated accurately and at stable body temperatures within the 50% interquartile of Tp (Tset) over the 72-hour period while the control group showed a more variable and lower Tp. Exposure to LPS negatively affected the BC of newborns, whereas it did not affect the BC of adult males. LPS challenges, used as a proxy of pathogen exposures to study lizard behavioral thermoregulation, constitute a practical approach to assess the immunological constraints lizards from high-latitude regions may face due to global warming and anthropogenic disturbances.
Topics: Infant, Newborn; Animals; Male; Humans; Lizards; Argentina; Lipopolysaccharides; Body Temperature Regulation; Temperature
PubMed: 37018837
DOI: 10.1590/0001-3765202320201923 -
Research Square Mar 2023Calcium is a critical signaling molecule in many cell types including immune cells. The calcium-release activated calcium channels (CRAC) responsible for store-operated...
Calcium is a critical signaling molecule in many cell types including immune cells. The calcium-release activated calcium channels (CRAC) responsible for store-operated calcium entry (SOCE) in immune cells are gated by STIM family members functioning as sensors of Ca store content in the endoplasmic reticulum. We investigated the effect of SOCE blocker BTP2 on human peripheral blood mononuclear cells (PBMC) stimulated with the mitogen phytohemagglutinin (PHA). We performed RNA sequencing (RNA-seq) to query gene expression at the whole transcriptome level and identified genes differentially expressed between PBMC activated with PHA and PBMC activated with PHA in the presence of BTP2. Among the differentially expressed genes, we prioritized genes encoding immunoregulatory proteins for validation using preamplification enhanced real time quantitative PCR assays. We performed multiparameter flow cytometry and validated by single cell analysis that BTP2 inhibits cell surface expression CD25 at the protein level. BTP2 reduced significantly PHA-induced increase in the abundance of mRNAs encoding proinflammatory proteins. Surprisingly, BTP2 did not reduce significantly PHA-induced increase in the abundance of mRNAs encoding anti-inflammatory proteins. Collectively, the molecular signature elicited by BTP2 in activated normal human PBMC appears to be tipped towards tolerance and away from inflammation.
PubMed: 36993646
DOI: 10.21203/rs.3.rs-2618144/v1