Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Innate immune responses in house dust mite allergy.

ABSTRACT: Sensitizations to house dust mites (HDM) trigger strong exacerbated allergen-induced inflammation of the skin and airways mucosa from atopic subjects resulting in atopic dermatitis as well as allergic rhinitis and asthma. Initially, the Th2-biased HDM allergic response was considered to be mediated only by allergen B- and T-cell epitopes to promote allergen-specific IgE production as well as IL-4, IL-5, and IL-13 to recruit inflammatory cells. But this general molecular model of HDM allergenicity must be revisited as a growing literature suggests that stimulations of innate immune activation pathways by HDM allergens offer new answers to the following question: what makes an HDM allergen an allergen? Indeed, HDM is a carrier not only for allergenic proteins but also microbial adjuvant compounds, both of which are able to stimulate innate signaling pathways leading to allergy. This paper will describe the multiple ways used by HDM allergens together with microbial compounds to control the initiation of the allergic response through engagement of innate immunity.

SUBMITTER: Jacquet A

PROVIDER: S-EPMC3658386 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Innate immune responses in house dust mite allergy.

Jacquet Alain A

ISRN allergy 20130228

Sensitizations to house dust mites (HDM) trigger strong exacerbated allergen-induced inflammation of the skin and airways mucosa from atopic subjects resulting in atopic dermatitis as well as allergic rhinitis and asthma. Initially, the Th2-biased HDM allergic response was considered to be mediated only by allergen B- and T-cell epitopes to promote allergen-specific IgE production as well as IL-4, IL-5, and IL-13 to recruit inflammatory cells. But this general molecular model of HDM allergenicit ...[more]

PMID: 23724247

Similar Datasets

Orchestrating house dust mite-associated allergy in the lung.

Project description:House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.

| S-EPMC3381841 | biostudies-literature

ADAMTS7 Attenuates House Dust Mite-Induced Airway Inflammation and Th2 Immune Responses.

Project description:PurposeADAMTS7 is a secreted metalloproteinase enzyme and proteoglycan associated with the early progression of coronary artery disease. However, there is limited information regarding the role of ADAMTS7 in lung adaptive immunity and inflammation. Thus, we sought to assess whether ADAMTS7 expression in the lung modulates house dust mite (HDM)-induced airway inflammation and Th2 immune response.MethodsThe role of ADAMTS7 in HDM-induced airway disease was assessed in ADAMTS7-deficient (ADAMTS7-/-) mice and compared with the wild-type control mice by flow cytometry, ELISA, and histopathology. Furthermore, the antigen priming capability of dendritic cells (DC) was determined ex vivo by employing coculture with CD4+ OT-II cells.ResultsADAMTS7-/- mice develop an augmented eosinophilic airway inflammation, mucous cell metaplasia, and increased Th2 immune response to inhaled HDM. In addition, allergen uptake by lung DC and migration to draining mediastinal lymph node were significantly increased in ADAMTS7-/- mice, which shows an enhanced capacity to mount allergen-specific T-cell proliferation and effector Th2 cytokine productions. We propose that the mechanism by which ADAMTS7 negatively regulates DC function involves attenuated antigen uptake and presentation capabilities, which reduces allergic sensitization and Th2 immune responses in the lung.ConclusionIn aggregate, we provide compelling evidence that ADAMTS7 plays a pivotal role in allergic airway disease and Th2 immunity and would be an attractive target for asthma.

| S-EPMC9205806 | biostudies-literature

House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins.

Project description:The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation.

| S-EPMC7924806 | biostudies-literature

Oral Exposure to House Dust Mite Activates Intestinal Innate Immunity.

Project description:House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.

| S-EPMC8000190 | biostudies-literature

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development.

Project description:Over 89% of asthmatic children in underdeveloped countries demonstrate sensitivity to house dust mites (HDMs). The allergic response to HDMs is partially mediated by epithelial cell-derived cytokines that activate group 2 innate lymphoid cells, induce migration and activation of dendritic cells, and promote effector differentiation of HDM-specific TH2 cells. However, the contribution of innate receptor engagement on epithelial or dendritic cells by HDMs that ultimately mediates said innate and adaptive allergic responses is poorly understood. We and other investigators have demonstrated that HDMs express phosphorylcholine (PC) moieties. The major PC receptors involved in immune responses include CD36 and platelet-activating factor receptor (PAFR). Because CD36 and PAFR are expressed by epithelial cells and dendritic cells, and expression of these receptors is higher in human asthmatics, we determined whether engagement of CD36 or PAFR on epithelial or dendritic cells contributes to HDM allergy development. Testing bone marrow chimeric mice revealed that CD36 engagement on radioresistant cells and PAFR engagement on radioresistant and radiosensitive cells in the lung promote allergic responses to HDMs. Additionally, passive anti-PC IgM Abs administered intratracheally with HDMs decreased allergen uptake by epithelial cells and APCs in the lungs of C57BL/6 mice but not CD36-/- or PAFR-/- mice. These results show that CD36 and PAFR are important mediators of HDM allergy development and that inhibiting HDM engagement with PC receptors in the lung protects against allergic airway disease.

| S-EPMC5538133 | biostudies-literature

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.

Project description:BACKGROUND:Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. OBJECTIVE:We sought to determine whether maternal HDM exposure influences asthma development in offspring. METHODS:Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, TH2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. RESULTS:Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, TH2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. CONCLUSIONS:Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma.

| S-EPMC5550362 | biostudies-literature

Neonatal exposure to pneumococcal phosphorylcholine modulates the development of house dust mite allergy during adult life.

Project description:Currently, ?20% of the global population suffers from an allergic disorder. Allergies and asthma occur at higher rates in developed and industrialized countries. It is clear that many human atopic diseases are initiated neonatally and herald more severe IgE-mediated disorders, including allergic asthma, which is driven by the priming of Th2 effector T cells. The hygiene hypothesis attempts to link the increased excessively sanitary conditions early in life to a default Th2 response and increasing allergic phenomena. Despite the substantial involvement of IgE Abs in such conditions, little attention has been paid to the effects of early microbial exposure on the B cell repertoire prior to the initiation of these diseases. In this study, we use Ab-binding assays to demonstrate that Streptococcus pneumoniae and house dust mite (HDM) bear similar phosphorylcholine (PC) epitopes. Neonatal C57BL/6 mice immunized with a PC-bearing pneumococcal vaccine expressed increased frequencies of PC-specific B cells in the lungs following sensitizing exposure to HDM as adults. Anti-PC IgM Abs in the lung decreased the interaction of HDM with pulmonary APCs and were affiliated with lowered allergy-associated cell infiltration into the lung, IgE production, development of airway hyperresponsiveness, and Th2 T cell priming. Thus, exposure of neonatal mice to PC-bearing pneumococci significantly reduced the development of HDM-induced allergic disease during adult life. Our findings demonstrate that B cells generated against conserved epitopes expressed by bacteria, encountered early in life, are also protective against the development of allergic disease during adult life.

| S-EPMC4456637 | biostudies-literature

The SQ House Dust Mite SLIT-Tablet Is Well Tolerated in Patients with House Dust Mite Respiratory Allergic Disease.

Project description:BackgroundThe SQ house dust mite (HDM) SLIT-tablet (ALK, Denmark) addresses the underlying cause of HDM respiratory allergic disease, and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma. Here, we present pooled safety data from an adult population with HDM respiratory allergy, with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile.MethodsSafety data from 2 randomised double-blind, placebo-controlled clinical trials were included: MT-04: 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis, and MT-06: 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma.ResultsThe proportion of subjects experiencing adverse events (AEs) was greater in the active treatment group (12 SQ-HDM; 73% of subjects) compared to placebo (53%). The most common treatment-related AEs were local allergic reactions. No AEs were reported as systemic allergic reactions. Regardless of asthma status, most AEs were mild or moderate (>97% of AEs) and the frequency of serious AEs was low. Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma (p = 0.88). In addition, subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma (p = 0.42).ConclusionThe SQ HDM SLIT-tablet is well tolerated, and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status.

| S-EPMC5804837 | biostudies-literature

Molecular characterization of Der p 10: a diagnostic marker for broad sensitization in house dust mite allergy.

Project description:Tropomyosins represent clinically relevant seafood allergens but the role of mite tropomyosin, Der p 10, in house dust mite (HDM) allergy has not been studied in detail.To express and purify a recombinant Der p 10 with equivalent IgE reactivity as natural Der p 10 and to evaluate its IgE reactivity and allergenic activity in HDM-allergic patients.rDer p 10 was expressed in Escherichia coli, purified and characterized by mass spectrometry and circular dichroism. It was tested for IgE reactivity in 1322 HDM-allergic patients. Detailed IgE-reactivity profiles to six HDM allergens (Der p 1, 2, 5, 7, 10, 21) were established for subgroups of Der p 10-positive and -negative patients. The allergenic activity of rDer p 10 was evaluated in basophil degranulation experiments.rDer p 10 is an ?-helical protein sharing IgE epitopes with nDer p 10. It is recognized by 15.2% of HDM-allergic patients. Der p 10-negative patients were primarily sensitized to Der p 1 and/or Der p 2, whereas Der p 10-positive patients reacted to several other HDM allergens besides the major allergens (Der p 1, Der p 2) or showed a rather selective Der p 10 reactivity. The allergenic activity of Der p 10 was generally low but patients could be identified who suffered from clinically relevant HDM allergy due to Der p 10 sensitization.Der p 10 may be a diagnostic marker for HDM-allergic patients with additional sensitization to allergens other than Der p 1 and Der p 2. Such patients may require attention when allergen-specific immunotherapy is considered.

| S-EPMC4642339 | biostudies-literature

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses.

Project description:Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells' (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-?B (NF-?B), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-?, and tumor necrosis factor (TNF)-? were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-?B, AP-1, and MAPK pathway. NECM induced IL-5, IFN-?, and TNF-? production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.

| S-EPMC7215961 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data