House Dust Mite Exposure Research Articles

House Dust Mite Exposure: Can It Be A Severe COVID-19 Prevention?

Background: In the midst of the ongoing COVID-19 pandemic, many studies are looking for treatment to suppress viral replication and prevention through vaccination. However, to this day the number of incidences and deaths due to COVID-19 is still increasing. Objective: The purpose of this article is to review theoretically the alleged increase in eosinophils in house dust mite exposure can prevent the severity of COVID-19 symptoms. Methods: This article was compiled through a literature search in reputable international journals by the time 2020-2021. Result: The severity of symptoms that arise due to COVID-19 infection is one of them caused by eosinophenia. On the other hand, the host immune response to house dust mite exposure can increase the number of eosinophils through stimulation of IL-6, IL-8, GM-CSF, IL-5 and IL-33. These eosinophils will then express TLR-7 on the cell surface which makes them able to recognize SARS-CoV-2. Stimulation of this eosinophil receptor triggers the production of cytokines, degranulation, superoxide, and nitric oxide (NO) through NO synthase which has a direct antiviral effect. EDN and ECP of human eosinophils can decrease viral infectivity through a ribonuclease-dependent mechanism. Eosinophils are capable of producing extracellular traps composed of eosinophilic granule proteins bound to mitochondrial DNA in response to viral infection in vitro, especially in an oxidative lung tissue environment. Eosinophils also rapidly mobilize granules of Th1 cytokines, including IL-12 and IFN-g which are important for antiviral immune responses. Conclusion: Although available data are still limited, there are indications that eosinophils have a protective effect during SARS-CoV-2 infection. Therefore, biological agents such as exposure to house dust mites targeting eosinophils may be useful to help clarify the role of eosinophils in their antiviral response.

Developing a Mobile Model for Controlled House Dust Mite Exposure

Allergen exposure chambers support clinical research by providing a controlled environment for investigation of allergic disease. While house dust mite (HDM) exposure chambers exist, expansion to multi-site clinical trials is inhibited by limited standardization across the small number of permanent facilities. We are developing HDM-allergen capability for a mobile naturalistic exposure chamber (mobile NEC) to facilitate expansion of HDM-allergy research.

House Dust Mite and Cat Dander Extract Induce Asthma-Like Histopathology with an Increase of Mucosal Mast Cells in a Guinea Pig Model.

Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs. Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells. Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells. We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.

Effect of birth season on allergic rhinitis and cedar pollinosis considering allergen and vitamin D exposure: The Japan Environment and Children's study (JECS)

BackgroundThe relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account. MethodsThis study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders. ResultsParticipants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13–3.82 for spring; aOR: 1.89, 95% CI: 1.03–3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10–2.15; Der f 1, aOR: 1.44, 95% CI: 1.03–2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively. ConclusionsSpring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required.

Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma

Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma in disease pathogenesis may expedite the development of novel targeted treatment strategies. In this study, we performed transcriptomics on the airway and parenchyma using a house dust mite (HDM)-induced model of experimental asthma that replicates key features of the human disease. HDM exposure increased the expression of 3,255 genes, of which 212 were uniquely increased in the airways, 856 uniquely increased in the parenchyma, and 2187 commonly increased in both compartments. Further interrogation of these genes using a combination of network and transcription factor enrichment analyses identified several transcription factors that regulate airway and/or parenchymal gene expression, including transcription factor EC (TFEC), transcription factor PU.1 (SPI1), H2.0-like homeobox (HLX), metal response element binding transcription factor-1 (MTF1) and E74-like factor 4 (ets domain transcription factor, ELF4) involved in controlling innate immune responses. We next assessed the effects of inhibiting lung SPI1 responses using commercially available DB1976 and DB2313 on key disease outcomes. We found that both compounds had no protective effects on airway inflammation, however DB2313 (8 mg/kg) decreased mucus secreting cell number, and both DB2313 (1 mg/kg) and DB1976 (2.5 mg/kg and 1 mg/kg) reduced small airway collagen deposition. Significantly, both compounds decreased airway hyperresponsiveness. This study demonstrates that SPI1 is important in HDM-induced experimental asthma and that its pharmacological inhibition reduces HDM-induced airway collagen deposition and hyperresponsiveness.

Avoidance measures for mite allergy—an update

AbstractHouse dust mites are a major source of allergens in house dust and, thus, the main trigger of perennial allergic respiratory diseases [1–5]. Scientific research on the life cycle, diet, and reproductive behavior of dust mites and on the biology of mite allergens has uncovered mechanisms leading to the development of respiratory allergies and suggests measures that can minimize exposure to dust mite allergens. Here, we discuss the evidence linking house dust mite exposure and respiratory allergies and present the efficacy of avoidance measures and their scientific evidence.

Delayed Microbial Maturation Durably Exacerbates Th17-driven Asthma in Mice.

Microbial maturation disrupted by early-life dysbiosis has been linked with increased asthma risk and severity; however, the immunological mechanisms underpinning this connection are poorly understood. We sought to understand how delaying microbial maturation drives worsened asthma outcomes later in life and its long-term durability. Drinking water was supplemented with antibiotics on Postnatal Days 10-20. To assess the immediate and long-term effects of delaying microbial maturation on experimental asthma, we initiated house dust mite exposure when bacterial diversity was either at a minimum or had recovered. Airway hyperresponsiveness, histology, pulmonary leukocyte recruitment, flow cytometric analysis of cytokine-producing lymphocytes, and assessment of serum IgG1 (Immunoglobulin G1) and IgE (Immunoglobulin E) concentrations were performed. RT-PCR was used to measure IL-13 (Interleukin 13)-induced gene expression in sequentially sorted mesenchymal, epithelial, endothelial, and leukocyte cell populations from the lung. Delayed microbial maturation increased allergen-driven airway hyperresponsiveness and Th17 frequency compared with allergen-exposed control mice, even when allergen exposure began after bacterial diversity recovered. Blockade of IL-17A (Interleukin 17A) reversed the airway hyperresponsiveness phenotype. In addition, allergen exposure in animals that experienced delayed microbial maturation showed signs of synergistic signaling between IL-13 and IL-17A in the pulmonary mesenchymal compartment. Delaying microbial maturation in neonates promotes the development of more severe asthma by increasing Th17 frequency, even if allergen exposure is initiated weeks after microbial diversity is normalized. In addition, IL-17A-aggravated asthma is associated with increased expression of IL-13-induced genes in mesenchymal, but not epithelial cells.

Explaining the polarized macrophage pool during murine allergic lung inflammation.

Differentially polarized macrophages, especially YM1+ and MHCII+ macrophages, play an important role in asthma development. The origin of these polarized macrophages has not been elucidated yet. We therefore aimed to investigate how proliferation, monocyte recruitment, and/or switching of polarization states contribute to this specific pool of polarized interstitial and alveolar macrophages during development of house dust mite (HDM)-induced allergic lung inflammation in mice. Male and female mice were first treated intranasally with PKH26 to label lung-resident macrophages and were then exposed to either HDM or phosphate-buffered saline (PBS) for two weeks. Different myeloid immune cell types were quantified in lung tissue and blood using flow cytometry. We found that macrophage polarization only starts up in the second week of HDM exposures. Before this happened, unpolarized alveolar and interstitial macrophages transiently increased in HDM-exposed mice. This transient increase was mostly local proliferation of alveolar macrophages, while interstitial macrophages also contained unlabeled macrophages suggesting monocyte contribution. After two weeks of exposures, the number of interstitial and alveolar macrophages was similar between HDM and PBS-exposed mice, but the distribution of polarization states was remarkably different. HDM-exposed mice selectively developed YM1+ alveolar macrophages and MHCII-hi interstitial macrophages while nonpolarized macrophages were lost compared to PBS-exposed mice. In this HDM model we have shown that development of a polarized macrophage pool during allergic inflammation is first dependent on proliferation of nonpolarized tissue-resident macrophages with some help of infiltrating unlabeled cells, presumably circulating monocytes. These nonpolarized macrophages then acquire their polarized phenotype by upregulating YM1 on alveolar macrophages and MHCII on interstitial macrophages. This novel information will help us to better understand the role of macrophages in asthma and designing therapeutic strategies targeting macrophage functions.

Alteration of glycosphingolipid metabolism by ozone is associated with exacerbation of allergic asthma characteristics in mice.

Asthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 h/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33-0.51 for females and R2 = 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.

Allergen-induced DNA release by the airway epithelium amplifies type 2 immunity

Alternaria alternata and house dust mite exposure evokes IL-33 secretion from the airway epithelium, which functions as an alarmin to stimulate type 2 immunity. Extracellular DNA (eDNA) is also an alarmin that intensifies inflammation in cystic fibrosis, chronic obstructive pulmonary disease, and asthma. We investigated the mechanisms underlying allergen-evoked DNA mobilization and release from the airway epithelium and determined the role of eDNA in type 2 immunity. Human bronchial epithelial (hBE) cells were used to characterize allergen-induced DNA mobilization and extracellular release using comet assays to measure DNA fragmentation, Qubit double-stranded DNA assays to measure DNA release, and DNA sequencing to determine eDNA composition. Mice were used to investigate the role of eDNA in type 2 immunity. Alternaria extract rapidly induces mitochondrial and nuclear DNA release from human bronchial epithelial cells, whereas house dust mite extract induces mitochondrial DNA release. Caspase-3 is responsible for nuclear DNA fragmentation and becomes activated after cleavage by furin. Analysis of secreted nuclear DNA showed disproportionally higher amounts of promotor and exon sequences and lower intron and intergenic regions compared to predictions of random DNA fragmentation. In mice, Alternaria-induced type 2 immune responses were blocked by pretreatment with a DNA scavenger. In caspase-3-deficient mice, Alternaria-induced DNA release was suppressed. Furthermore, intranasal administration of mouse genomic DNA with Alternaria amplified secretion of IL-5 and IL-13 into bronchoalveolar lavage fluid while DNA alone had no effect. These findings highlight a novel, allergen-induced mechanism of rapid DNA release that amplifies type 2 immunity in airways.

Targeting an Initiator Allergen Provides Durable and Expansive Protection against House Dust Mite Allergy.

Whereas treatment of allergic diseases such as asthma relies largely on the targeting of dysregulated effector pathways, the conceptually attractive alternative of preventing them by a pharmaceutical, at-source intervention has been stymied until now by uncertainties about suitable targets and the challenges facing drug design. House dust mites (HDMs) are globally significant triggers of allergy. Group 1 HDM allergens, exemplified by Der p 1, are cysteine proteases. Their degradome has a strong disease linkage that underlies their status as risk and initiator allergens acting directly and through bystander effects on other allergens. Our objective was to test whether target-selective inhibitors of group 1 HDM allergens might provide a viable route to novel therapies. Using structure-directed design to optimize a series of pyruvamides, we undertook the first examination of whether pharmaceutically developable inhibitors of group 1 allergens might offer protection against HDM exposure. Developability criteria included durable inhibition of clinically relevant signals after a single aerosolized dose of the drug. The compounds suppressed acute airway responses of rats and mice when challenged with an HDM extract representing the HDM allergome. Inhibitory effects operated through a miscellany of downstream pathways involving, among others, IL-33, thymic stromal lymphopoietin, chemokines, and dendritic cells. IL-13 and eosinophil recruitment, indices of Th2 pathway activation, were strongly attenuated. The surprisingly expansive benefits arising from a unique at-source intervention suggest a novel approach to multiple allergic diseases in which HDMs play prominent roles and encourage exploration of these pharmaceutically developable molecules in a clinical setting.

Role of ventilation and cleaning for controlling house dust mite allergen infestation: A study on associations of house dust mite allergen concentrations with home environment and life styles in Tianjin area, China.

House dust mites produce well-known allergens for asthma and allergy among children. To study house dust mite allergen exposure level in northeast China and characterize its association with indoor environmental factors and cleaning habits, we inspected 399 homes in Tianjin area and collected dust from mattresses. Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p) were detected by the enzyme-linked immunosorbent assay (ELISA) method. The medians of total allergen concentrations for spring, summer, autumn, and winter were 524 ng/g, 351 ng/g, 1022 ng/g, and 1010 ng/g. High indoor air relative humidity (RH), low air change rate, indoor dampness, and frequent changing of quilt cover/bedsheet/pillow case were significantly associated with high house dust mite allergen concentration (relative risk [RR]: RH, 1.18-1.34; air change rate, 0.97-1.00; dampness, 2.92-3.83; changing quilt cover/bedsheet/pillow case, 0.66-0.75). The decrease in the absolute humidity gradient between indoors and outdoors that occurs with increased air change rate may explain why a high ventilation reduces house dust mite allergen concentration. The findings of this study show the importance of ventilation and cleaning for controlling house dust mite allergens. We found that the decrease in additional absolute humidity (e.g., humidity indoor -humidity outdoor ) with increased air change rate may be the main reason that a high ventilation rate reduces house dust mite allergen concentration. Ventilation and cleaning should be both considered for creating a healthy home environment.

In utero exposures to mint-flavored JUUL aerosol impair lung development and aggravate house dust mite-induced asthma in adult offspring mice

There are few reports concerning electronic nicotine delivery system (ENDS) use during pregnancy and no studies on asthma in prenatally JUUL-exposed offspring. Here, we tested the hypothesis that in utero JUUL exposure causes unfavorable birth outcomes and lasting pulmonary health effects in adult offspring. BALB/c dams were exposed to either air or mint-flavored JUUL aerosol, 1-hr/d, 20 consecutive days during gestation. Offspring were sacrificed on post-natal day (PND) 0 or at 11-week of age, following house dust mite (HDM) challenge. Gene expression was assessed in the uterine/placental tissue of the dams and lung responses were assessed in offspring at PND0 and at 11 weeks of age. JUUL-exposed offspring exhibited decreased body weights and lengths at PND0. These birth outcomes were accompanied by dysregulation of 54 genes associated with hypoxia and oxidative stress in the uterine/placental tissues of JUUL-exposed dams, as well as 24 genes in the lungs of the offspring related to Wnt signaling, plus 9 genes related to epigenetics, and 7 genes related to inflammation. At 11 weeks of age, JUUL + HDM exposed mice exhibited pulmonary inflammation when compared to their respective air + HDM controls. Additionally, the JUUL + HDM exposure dysregulated several genes associated with allergies and asthma. Further, the JUUL + HDM females showed decreased methylation of the promoter region of the Il10ra gene. Taken together, our mouse model shows that inhalation of JUUL aerosols during pregnancy affects the intrauterine environment, impairs lung development, and heightens the effects of allergic airway responses later in life.

HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma.

Asthma is a disease characterized by airway epithelial barrier destruction, chronic airway inflammation, and airway remodeling. Repeated damage to airway epithelial cells by allergens in the environment plays an important role in the pathophysiology of asthma. Ferroptosis is a novel form of regulated cell death mediated by lipid peroxidation in association with free iron-mediated Fenton reactions. In this study, we explored the contribution of ferroptosis to house dust mite (HDM)-induced asthma models. Our in vivo and in vitro models showed labile iron accumulation and enhanced lipid peroxidation with concomitant nonapoptotic cell death upon HDM exposure. Treatment with ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1) illuminated the role of ferroptosis and related damage-associated molecular patterns in HDM-treated airway epithelial cells. Furthermore, DFO and Fer-1 reduced HDM-induced airway inflammation in model mice. Mechanistically, NCOA4-mediated ferritin-selective autophagy (ferritinophagy) was initiated during ferritin degradation in response to HDM exposure. Together, these data suggest that ferroptosis plays an important role in HDM-induced asthma and that ferroptosis may be a potential treatment target for HDM-induced asthma.

Exogenous leptin enhances markers of airway fibrosis in a mouse model of chronic allergic airways disease

BackgroundAsthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.MethodsFive-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6–9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson’s trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.ResultsLeptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.ConclusionsIn HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.

House Dust Mite Exposure through Human Milk and Dust: What Matters for Child Allergy Risk?

Allergies are major noncommunicable diseases associated with significant morbidity, reduced quality of life, and high healthcare costs. Despite decades of research, it is still unknown if early-life exposure to indoor allergens plays a role in the development of IgE-mediated allergy and asthma. The objective of this study is to contribute to the identification of early-life risk factors for developing allergy. We addressed whether two different sources of house dust mite Der p 1 allergen exposure during early life, i.e., human milk and dust, have different relationships with IgE levels and asthma outcomes in children. We performed longitudinal analyses in 249 mother–child pairs using data from the PIAMA birth cohort. Asthma symptoms and serum total and specific IgE levels in children were available for the first 16 years of life. Der p 1 levels were measured in human milk and dust samples from infant mattresses. We observed that infant exposure to Der p 1 through human milk was associated with an increased risk of having high levels of serum IgE (top tertile > 150 kU/mL) in childhood as compared to infants exposed to human milk with undetectable Der p 1 [adjusted OR (95% CI) 1.83 (1.05–3.20) p = 0.0294]. The Der p 1 content in infant mattress dust was not associated with increased IgE levels in childhood. The risk of asthma and Der p 1 sensitization was neither associated with Der p 1 in human milk nor with Der p 1 in dust. In conclusion, high levels of IgE in childhood were associated with Der p 1 exposure through human milk but not exposure from mattress dust. This observation suggests that human milk is a source of Der p 1 exposure that is relevant to allergy development and fosters the need for research on the determinants of Der p 1 levels in human milk.

6-gingerol attenuates pulmonary inflammation and oxidative stress in mice model of house dust mite-induced asthma

Asthma is a chronic non-communicable inflammatory disease of the lung that affects over 300 million people worldwide. 6-Gingerol (6-G) is a phytocompound found in ginger rhizome that has been reported to exhibit anti-inflammatory effects. However, there is paucity of information regarding the effect of 6-G on asthma. This study was designed to evaluate the effect of 6-G on house dust mite (HDM) -induced asthma. Male mice were divided into 5 groups of 10 mice each. Group 1 served as control; group 2 received 6-G (10 mg/kg/day) for 5 weeks. Group 3 received HDM (10 µg/kg/day) for 4 weeks. Group 4 received 6-G (10 mg/kg/day) for 1 week prior to co-exposure with HDM (10 µg/kg/day) for 4 weeks, and group 5 received Dexamethasone (DEX) (1 mg/kg/day) and HDM (10 µg/kg/day) for 4 weeks. Administration of HDM significantly increased lymphocytes, leukocytes, neutrophils, eosinophils, myeloperoxidase (MPO), nitric oxide (•NO), malondialdehyde, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and decreased the activities of superoxide dismutase (SOD), catalase, glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione (GSH) and ascorbic acid (AA) levels relative to control. Administration of 6-G and DEX prior to HDM exposure significantly decreased lymphocytes, leukocytes, neutrophils, eosinophils, MPO, •NO, malondialdehyde, TNF-α, IL-6 and increased the activities of SOD, catalase, GST, GPx, and levels of GSH and AA relative to HDM group. Histopathological examination of the lungs of HDM-treated mice showed the presence of oedema and inflammation of the bronchi and alveoli. Administration of 6-G and DEX reversed these lesions. 6-G ameliorated House dust mite-induced asthma via anti-inflammatory and anti-oxidant mechanism.

Unique Allergic Asthma Phenotypes in Offspring of House Dust Mite-exposed Mice.

Asthma is a heterogeneous inflammatory airway disease that develops in response to a combination of genetic predisposition and environmental exposures. Patients with asthma are grouped into phenotypes with shared clinical features and biomarker profiles to help tailor specific therapies. However, factors driving development of specific phenotypes are poorly understood. Prenatal exposure to maternal asthma is a unique risk factor for childhood asthma. Here we tested whether maternal asthma skews asthma phenotypes in offspring. We compared airway hyperreactivity and inflammatory and neurotrophin lung signatures before and after allergen challenge in offspring born to mice exposed to house dust mite (HDM) or vehicle during pregnancy. Maternal HDM exposure potentiated offspring responses to HDM allergen, significantly increasing both airway hyperreactivity and airway eosinophilia compared with control mice. Maternal HDM exposure broadly skewed the offspring cytokine response from a classic allergen-induced T-helper cell type 2 (Th2)-predominant signature in HDM-treated offspring of vehicle-exposed mothers, toward a mixed Th17/Th1 phenotype in HDM-treated offspring of HDM-exposed mothers. Morphologic analysis determined that maternal HDM exposure also increased airway epithelial sensory nerve density and induced distinct neurotrophin signatures to support airway hyperinnervation. Our results demonstrate that maternal allergen exposure alters fetal lung development and promotes a unique inflammatory phenotype at baseline and in response to allergen that persists into adulthood.

Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract.

Excessive production, secretion, and retention of abnormal mucus is a pathological feature of many obstructive airways diseases including asthma. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in asthma. The current study investigated these nonantibiotic activities of azithromycin in mice exposed daily to intranasal house dust mite (HDM) extract for 10 days. HDM-exposed mice exhibited airways hyperresponsiveness to aerosolized methacholine, a pronounced mixed eosinophilic and neutrophilic inflammatory response, increased airway smooth muscle (ASM) thickness, and elevated levels of epithelial mucin staining. Azithromycin (50 mg/kg sc, 2 h before each HDM exposure) attenuated HDM-induced airways hyperresponsiveness to methacholine, airways inflammation (bronchoalveolar lavage eosinophil and neutrophils numbers, and IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, and RANTES levels), and epithelial mucin staining (mucous metaplasia) by at least 50% (compared with HDM-exposed mice, P < 0.05). Isolated tracheal segments of HDM-exposed mice secreted Muc5ac and Muc5b (above baseline levels) in response to exogenous ATP. Moreover, ATP-induced secretion of mucins was attenuated in segments obtained from azithromycin-treated, HDM-exposed mice (P < 0.05). In additional ex vivo studies, ATP-induced secretion of Muc5ac (but not muc5b) from HDM-exposed tracheal segments was inhibited by in vitro exposure to azithromycin. In vitro azithromycin also inhibited ATP-induced secretion of Muc5ac and Muc5b in tracheal segments from IL-13-exposed mice. In summary, azithromycin inhibited ATP-induced mucin secretion and airways inflammation in HDM-exposed mice, both of which are likely to contribute to suppression of airways hyperresponsiveness.

House dust mite exposure enhances immune responses to ovalbumin-induced intestinal allergy

House dust mites (HDM) are one of the important factors of airway allergic diseases, HDM allergens can be detected in the human gut mucosa, which induces local inflammation and increases intestinal epithelial permeability. This study tests a hypothesis that HDM contribute to the development of OVA (ovalbumin)-induced intestinal allergy. The serum levels of IgE against HDM in patients with food allergy were detected with UniCAP100 (Pharmacia, Uppsala, Sweden); a mouse model of food allergy was developed with OVA and HDM as the specific antigens. Compared to healthy controls, patients with food allergy have higher levels of serum HDM-specific IgE. Compared to food allergy alone groups, the levels of HDM-specific IgE in patients with food allergy and asthma or allergic rhinitis were significantly higher. In mouse models, we found that HDM/OVA induced allergy-like symptoms, lower body temperature, and lower body weight. The levels of IgE, IgG1, mMCP-1 (mouse mast cell protease-1), IL-4 and IL-5 in the HDM and HDM + CT (cholera toxin) groups were higher than the control groups, and the levels of IgE, IgG1, IL-4 and IL-5 in the HDM, OVA and HDM + OVA groups were higher than the control groups. The pathological changes of intestinal tissues in the HDM and HDM + CT/the HDM, OVA and HDM + OVA groups were more severe, more eosinophil infiltration than the control groups. Moreover, exposure to HDM induced intestinal barrier dysfunction, and facilitated the development of intestinal allergy in mice. In conclusion, HDM exposure enhances immune responses to OVA-induced food allergy.