scholarly journals Helminth infection induces non-functional sensitization to house dust mites

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253887
Author(s):  
Virginie Doyen ◽  
Carine Truyens ◽  
Hoa Nhu Thi ◽  
Hiep Tran Thi Mong ◽  
Thanh Le Chi ◽  
...  
Keyword(s):  
Mast Cells ◽  
Helminth Infection ◽  
Clinical Symptoms ◽  
Allergic Sensitization ◽  
Humoral Response ◽  
House Dust Mites ◽  
Helminth Infections ◽  
Major Allergens ◽  
Ige Response

Background IgE characterizes the humoral response of allergic sensitization but less is known about what modulates its function and why some patients present clinical symptoms for a given IgE level and others do not. An IgE response also occurs during helminth diseases, independently of allergic symptoms. This response could be a model of non-functional IgE. Objective To study the IgE response against environmental allergens induced during natural helminth infection. Methods In 28 non allergic subjects from the periphery of Ho Chi Minh city with (H+, n = 18) and without helminth infection (H-, n = 10), we measured IgE and IgG4 against several components of Dermatophagoïdes pteronyssinus (Dpt) and Ascaris (a marker of immunization against nematodes), and determined the IgE component sensitization profile using microarray ISAC biochips. The functional ability of IgE to induce degranulation of cultured mast cells was evaluated in the presence of Dpt. Results Non allergic H+ subjects exhibited higher levels of IgE against Dpt compared to H- subjects. Dpt IgE were not functional in vitro and did not recognize usual Dpt major allergens. IgE recognized other component allergens that belong to different protein families, and most were glycosylated. Depletion of IgE recognizing carbohydrate cross-reactive determinant (CCD) did not induce a reduction in Dpt IgE. The Dpt IgG4 were not significantly different. Conclusion Helminth infections induced IgE against allergens such as Dpt and molecular components that belong to different sources as well as against CCD (such as β-1,2-xylose and/or ⍺-1,3-fucose substituted N-glycans). Dpt IgE were not able to induce degranulation of mast cells and were not explained by sensitization to usual major allergens or N-glycans.

scholarly journals Macrophage Activation and Functions during Helminth Infection: Recent Advances from the Laboratory Mouse

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Marion Rolot ◽  
Benjamin G. Dewals
Keyword(s):  
Immune Responses ◽  
Helminth Infection ◽  
Laboratory Mouse ◽  
Alternative Activation ◽  
Recent Advances ◽  
Helminth Infections ◽  
Classically Activated Macrophages

Macrophages are highly plastic innate immune cells that adopt an important diversity of phenotypes in response to environmental cues. Helminth infections induce strong type 2 cell-mediated immune responses, characterized among other things by production of high levels of interleukin- (IL-) 4 and IL-13. Alternative activation of macrophages by IL-4 in vitro was described as an opposite phenotype of classically activated macrophages, but the in vivo reality is much more complex. Their exact activation state as well as the role of these cells and associated molecules in type 2 immune responses remains to be fully understood. We can take advantage of a variety of helminth models available, each of which have their own feature including life cycle, site of infection, or pathological mechanisms influencing macrophage biology. Here, we reviewed the recent advances from the laboratory mouse about macrophage origin, polarization, activation, and effector functions during parasitic helminth infection.

scholarly journals Caspase-11 regulates lung inflammation in response to house dust mites

2020 ◽  
Author(s):  
Arwa Abu khweek ◽  
Marisa R. Joldrichsen ◽  
Eunsoo Kim ◽  
Zayed Attia ◽  
Kathrin Krause ◽  
...  
Keyword(s):  
House Dust ◽  
Inflammatory Responses ◽  
Allergic Sensitization ◽  
Allergic Inflammation ◽  
House Dust Mites ◽  
Host Responses ◽  
Dust Mites ◽  
Molecular Patterns

Abstract Asthma is an inflammatory lung disorder characterized by mucus hypersecretion, cellular infiltration, and bronchial hyper-responsiveness. House dust mites (HDM) are the most prevalent cause of allergic sensitization. Canonical and noncanonical inflammasomes are multiprotein complexes that assemble in response to pathogen or danger-associated molecular patterns (PAMPs or DAMPs). Murine caspase-11 engages the noncanonical inflammasome. We addressed the role of caspase-11 in mediating host responses to HDM and subsequent allergic inflammation using caspase-11−/− mice, which lack caspase-11 while express caspase-1. We found that HDM induce caspase-11 expression in vitro. The presence of IL-4 and IL-13 promotes caspase-11 expression. Additionally, caspase-11−/− macrophages show reduced release of (KC, IL-6 and IL-12) cytokines, and express lower levels of costimulatory molecules (e.g., CD40, CD86 and MHCII) in response to HDM stimulation. Notably, HDM sensitization of caspase-11−/− mice resulted in similar levels of IgE responses and hypothermia in response to nasal HDM challenge compared to WT. However, analysis of cell numbers and cytokines in bronchiolar alveolar fluid (BALF), as well as histological lung tissue showed altered inflammatory responses and reduced neutrophilia in the airways of the caspase-11−/− mice. These findings indicate that caspase-11 regulates airway inflammation in response to HDM exposure.

scholarly journals Helminth Infection Increases the Probability of Indeterminate QuantiFERON Gold in Tube Results in Pregnant Women

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Dawit Gebreegziabiher ◽  
Kassu Desta ◽  
Rawleigh Howe ◽  
Markos Abebe
Keyword(s):  
Helminth Infection ◽  
Cross Sectional Study ◽  
World Population ◽  
Indeterminate Result ◽  
Cross Sectional ◽  
Helminth Infections ◽  
Three Samples ◽  
Mycobacterial Antigens ◽  
Pregnant Mothers

Background.Approximately one-third of the world population is infected withM. tuberculosisand helminths (Kariminia et al. (2009), Walson et al. (2010)). Pregnancy and Helminth infection are known to suppress theTH1response (Kariminia et al. (2009), Elias et al. (2006)) on which the QuantiFERON Gold in Tube (QFT-GIT) assay, that measures the released IFN-γuponin vitrostimulation with mycobacterial antigens, relies on (Thomas et al. (2010)).Objective.To determine whether QFT-GIT indeterminate result is significantly associated with helminth infection or not.Methods.In this cross-sectional study, eighty-five pregnant mothers were screened for parasitic and LTBI using Kato-Katz and QFT-GIT test-respectively,Result.The prevalence of helminth infection in pregnant mothers was 23 (27%) of this 17 (20%) was due toSchistosoma mansoni. Among the total of 85 study participants 26.8% were QFT-GIT positive and 14 (17%) had indeterminate results. Three samples (21.4%) were randomly selected from the indeterminate QFT-GIT results and retested to check the reproducibility of the assay and remained indeterminate. QFT-GIT indeterminate result showed significant association with helminth infection.Conclusion.Helminth infections were significantly associated with indeterminate QFT-GIT results in pregnant mothers. Therefore further study is important to evaluate the possible effect of helminth infection by excluding the effect of pregnancy, as pregnancy also downregulates cellular immunity.

scholarly journals Chronic Wasting Due to Liver and Rumen Flukes in Sheep

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 549
Author(s):  
Alexandra Kahl ◽  
Georg von Samson-Himmelstjerna ◽  
Jürgen Krücken ◽  
Martin Ganter
Keyword(s):  
Fasciola Hepatica ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Infection Intensity ◽  
Liver Parenchyma ◽  
Trematode Species ◽  
Helminth Infections ◽  
Juvenile Worm ◽  
Juvenile Stages ◽  
Common Liver Fluke

Grazing sheep and goats are constantly exposed to helminth infections in many parts of the world, including several trematode species that causes a range of clinical diseases. The clinical picture of flukes is dependent upon the organs in which they develop and the tissues they damage within the respective organs. Accordingly, infections with the common liver fluke Fasciola hepatica, which, as juvenile worm migrates through the liver parenchyma for several weeks, may be associated with hepatic disorders such as impairment of carbohydrate, protein and fat metabolism, followed by chronic wasting. In contrast, the lancet fluke Dicrocoelium dendriticum, which does not exhibit tissue migration and thus does not lead to major tissue damage and bleeding, also does not lead to significant clinical symptoms. Rumen flukes such as Cotylophoron daubneyi cause catarrhal inflammation during their migration through the intestinal and abomasal epithelium during its juvenile stages. Depending on the infection intensity this may result in a range of clinical symptoms including diarrhoea, inappetence or emaciation. In this review, we aim to provide an update on the current knowledge on flukes particularly concerning the clinical relevance of the most important fluke species in sheep.

scholarly journals In vitro testing of explanted shunt valves in hydrocephalic patients with suspected valve malfunction

2021 ◽  
Author(s):  
Christoph Bettag ◽  
Christian von der Brelie ◽  
Florian Baptist Freimann ◽  
Ulrich-Wilhelm Thomale ◽  
Veit Rohde ◽  
...  
Keyword(s):  
Flow Rate ◽  
Clinical Symptoms ◽  
Obstructive Hydrocephalus ◽  
Flow Characteristics ◽  
Normal Pressure ◽  
Diagnostic Tools ◽  
Programmable Valve ◽  
Significant Difference ◽  
Valve Malfunction

AbstractDiagnosis of symptomatic valve malfunction in hydrocephalic patients treated with VP-Shunt (VPS) might be difficult. Clinical symptoms such as headache or nausea are nonspecific, hence cerebrospinal fluid (CSF) over- or underdrainage can only be suspected but not proven. Knowledge concerning valve malfunction is still limited. We aim to provide data on the flow characteristics of explanted shunt valves in patients with suspected valve malfunction. An in vitro shunt laboratory setup was used to analyze the explanted valves under conditions similar to those in an implanted VPS. The differential pressure (DP) of the valve was adjusted stepwise to 20, 10, 6, and 4 cmH2O. The flow rate of the explanted and the regular flow rate of an identical reference valve were evaluated at the respective DPs. Twelve valves of different types (Codman CertasPlus valve n = 3, Miethke Shuntassistant valve n = 4, Codman Hakim programmable valve n = 3, DP component of Miethke proGAV 2.0 valve n = 2) from eight hydrocephalic patients (four male), in whom valve malfunction was assumed between 2016 and 2017, were replaced with a new valve. Four patients suffered from idiopathic normal pressure (iNPH), three patients from malresorptive and one patient from obstructive hydrocephalus. Post-hoc analysis revealed a significant difference (p < 0.001) of the flow rate between each explanted valve and their corresponding reference valve, at each DP. In all patients, significant alterations of flow rates were demonstrated, verifying a valve malfunction, which could not be objectified by the diagnostic tools used in the clinical routine. In cases with obscure clinical VPS insufficiency, valve deficiency should be considered.

Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy

2021 ◽  
Author(s):  
Jiapan Gao ◽  
Delu Che ◽  
Xueshan Du ◽  
Yi Zheng ◽  
Huiling Jing ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Mast Cells ◽  
Pharmaceutical Products ◽  
Drug Induced ◽  
Inflammatory Infiltration ◽  
Local Inflammatory Response ◽  
Allergic Contact ◽  
G Protein Coupled

Abstract Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.

scholarly journals NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Fabrizio Gardoni ◽  
Jennifer Stanic ◽  
Diego Scheggia ◽  
Alberto Benussi ◽  
Barbara Borroni ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
In Vivo Studies ◽  
Ionotropic Glutamate Receptors ◽  
Brain Disorders ◽  
Functional Impairments ◽  
Different Types

The role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. Several in vitro and in vivo studies performed in the last decade have dramatically improved our understanding of the molecular and functional effects induced by both NMDAR and AMPAR autoantibodies at the excitatory glutamatergic synapse and, consequently, their possible role in the onset of clinical symptoms. In particular, the method by which autoantibodies can modulate the localization at synapses of specific target subunits leading to functional impairments and behavioral alterations has been well addressed in animal studies. Overall, these preclinical studies have opened new avenues for the development of novel pharmacological treatments specifically targeting the synaptic activation of ionotropic glutamate receptors.

Induction of leukotriene production by bleomycin and asparaginase in mast cells in vitro and in patients in vivo

1998 ◽  
Vol 55 (4) ◽  
pp. 447-453 ◽  
Author(s):  
Susanne Geuenich ◽  
Christopher Haberl ◽  
Dietmar Egger ◽  
Uwe Kaspers ◽  
Lothar Hültner ◽  
...  
Keyword(s):  
Mast Cells

PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 752-759 ◽  
Author(s):  
Karoline V. Gleixner ◽  
Matthias Mayerhofer ◽  
Karl J. Aichberger ◽  
Sophia Derdak ◽  
Karoline Sonneck ◽  
...  
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Drug Effects ◽  
Kit Mutation ◽  
Growth Inhibitory ◽  
Ic50 Values ◽  
Tk Inhibitors ◽  
Mast Cell Leukemia ◽  
Kit D816v

AbstractIn most patients with systemic mastocytosis (SM), including aggressive SM and mast cell leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V. KIT D816V is associated with constitutive tyrosine kinase (TK) activity and thus represents an attractive drug target. However, imatinib and most other TK inhibitors fail to block the TK activity of KIT D816V. We show that the novel TK-targeting drugs PKC412 and AMN107 counteract TK activity of D816V KIT and inhibit the growth of Ba/F3 cells with doxycycline-inducible expression of KIT D816V as well as the growth of primary neoplastic mast cells and HMC-1 cells harboring this KIT mutation. PKC412 was a superior agent with median inhibitory concentration (IC50) values of 50 to 250 nM without differences seen between HMC-1 cells exhibiting or lacking KIT D816V. By contrast, AMN107 exhibited more potent effects in KIT D816V- HMC-1 cells. Corresponding results were obtained with Ba/F3 cells exhibiting wild-type or D816V-mutated KIT. The growth-inhibitory effects of PKC412 and AMN107 on HMC-1 cells were associated with induction of apoptosis and down-regulation of CD2 and CD63. PKC412 was found to cooperate with AMN107, imatinib, and cladribine (2CdA) in producing growth inhibition in HMC-1, but synergistic drug interactions were observed only in cells lacking KIT D816V. Together, PKC412 and AMN107 represent promising novel agents for targeted therapy of SM. (Blood. 2006;107: 752-759)

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