House Dust Mite Exposure Research Articles

Targeted micronutrition via holo-BLG based on the farm effect in house dust mite allergic rhinoconjunctivitis patients – first evaluation in a standardized allergen exposure chamber

Abstract Purpose Evaluation of a lozenge for targeted micronutrition (holo-BLG), a new invention based on the farm effect, in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients in a standardized allergen exposure chamber (AEC). Methods Eligible HDM allergic patients were exposed to HDM raw material in an AEC for 120 min before (V1) and after (V3) 3 months of holo-BLG supplementation. Nasal, conjunctival, bronchial and other symptoms were rated by the patients every 10 min and, wellbeing, peak nasal inspiratory flow (PNIF), and lung function parameters every 30 min. Primary endpoint was the change in median Total Nasal Symptom Score (TNSS) at V3 compared to V1 at 120 min of exposure. Secondary endpoints consisted of the exploratory analysis of the temporal evolution of symptom scores using linear mixed effects models. Results A total of 32 patients were included in the analysis. A significant improvement of 60% (p = 0.0034) in the primary endpoint TNSS (V1 2.5 [interquartile range, IQR 1–4], V3 1.0 [IQR 1–3]) was observed. 40% improvement was seen for the Total Symptom Score (V1 5.0 [IQR 3–9], V3 3.0 [IQR 2–4]; [Wilcoxon test: confidence interval 1.5–4.0, p < 0.0003]). The analysis of the temporal evolution of all symptom scores and the personal wellbeing revealed clinically meaningful improvement over time, manifested in a lower symptom increase during the final HDM exposure. No relevant differences were observed for PNIF and lung function parameters. Safety and tolerability were rated as excellent. Conclusions The effect of holo-BLG resulting in immune resilience might help to fight the allergy epidemic on a new front based on targeted micronutrition of immune cells. Trial registration The study was retrospectively registered at clinicaltrials.gov (NCT04477382).

Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.

Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [Dermatophagoides pteronyssinus extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process. Lung sections were immunohistochemically stained for CD42b+ platelets. Intravital microscopy in allergic mice was used to visualize platelets tagged with an anti–mouse CD49b-PE (phycoerythrin) antibody. Platelet–endothelial interactions were measured in response to HDM (DerP1) exposure in the presence of antagonists to CCR3, CCR4, and CXCR4. Extravascular CD42b+ platelets were detected in the epithelium and submucosa in bronchial biopsy specimens taken from subjects with steroid-naive mild asthma. Platelets were significantly raised in the lung parenchyma from patients with fatal asthma compared with postmortem control-lung tissue. Furthermore, in DerP1-sensitized mice, subsequent HDM exposure induced endothelial rolling, endothelial adhesion, and recruitment of platelets into airway walls, compared with sham-sensitized mice, via a CCR3-dependent mechanism in the absence of aggregation or interactions with leukocytes. Localization of singular, nonaggregated platelets occurs in lungs of patients with asthma. In allergic mice, platelet recruitment occurs via recognized vascular adhesive and migratory events, independently of leukocytes via a CCR3-dependent mechanism.

Carboxypeptidase inhibition by NvCI suppresses airway hyperreactivity in a mouse asthma model

Carboxypeptidase inhibition by NvCI suppresses airway hyperreactivity in a mouse asthma model

Effective Ways to Prevent Allergic Diseases: Where Do We Stand?

Since allergic diseases are of great public health relevance, effective primary prevention strategies are urgently needed. This chapter gives an overview of existing primary prevention programs on environmental exposures and dietary strategies based on epidemiological studies which have defined risk- and protective factors for the development of allergic diseases.The allergy protective effect mediated by growing up on a traditional farm environment is well studied. But the exact underlying mechanisms have still not been fully clarified and have not yet led to concrete prevention strategies. The beneficial effect of avoiding cigarette smoke exposure, indoor moisture and molds in pregnancy and childhood on the development of asthma is well documented. Whereas the avoidance of house dust mite exposure is not recommended to prevent eczema or allergy. Dietary supplementation with vitamins, pre- and probiotics in pregnant woman and their offspring is not harmful but evidence for the prevention of allergic diseases is still lacking. Fish oil consumption was shown to be asthma protective. The early introduction of peanuts and egg protein to prevent peanut and egg allergy in children with atopic dermatitis is promising. Further studies are needed to increase the overall evidence in allergy prevention. Most studies lack methodological standards such as randomization and blinding. More evidence is in demand on the potential beneficial impact of multifaceted interventional studies. The future of allergy prevention strategies might be based on individual risk assessment. Therefore, research in the immunological and molecular basis of allergic diseases needs to be promoted.

Lrp1 Regulation of Pulmonary Function. Follow-Up of Human GWAS in Mice.

Human genome-wide association studies (GWASs) have identified more than 270 loci associated with pulmonary function; however, follow-up studies to determine causal genes at these loci are few. SNPs in low-density lipoprotein receptor-related protein 1 (LRP1) are associated with human pulmonary function in GWASs. Using murine models, we investigated the effect of genetic disruption of the Lrp1 gene in smooth muscle cells on pulmonary function in naive animals and after exposure to bacterial LPS or house dust mite extract. Disruption of Lrp1 in smooth muscle cells leads to an increase in tissue resistance, elastance, and tissue elastance at baseline. Furthermore, disruption of Lrp1 in smooth muscle increases airway responsiveness as measured by increased total lung resistance and airway resistance after methacholine. Immune cell counts in BAL fluid were increased in animals with Lrp1 disruption. The difference in airway responsiveness by genotype observed in naive animals was not observed after LPS or house dust mite extract exposure. To further explore the mechanisms contributing to changes in pulmonary function, we identified several ligands dysregulated with Lrp1 disruption in smooth muscle cells. These data suggest that dysregulation of LRP1 in smooth muscle cells affects baseline pulmonary function and airway responsiveness and helps establish LRP1 as the causal gene at this GWAS locus.

Peri-adolescent asthma: Acute impacts on innate immune response, corticosterone, and microglia in mice

Asthma is highly comorbid with anxiety in youth. We investigated the hypothalamic-pituitary-adrenal (HPA) axis and microglia as mechanisms underlying asthma and anxiety comorbidity. We induced asthma symptoms in developing BALB/cJ mice with house dust mite (HDM) for airway inflammation and methacholine (MCH) for bronchoconstriction. On the last day of exposure, we analyzed samples at six timepoints. Lung IL-5 and IL-1β expression peaked 4 h after final HDM exposure. Circulating corticosterone was blunted in a sex- and treatment-specific temporal pattern. Hippocampal IL-1β expression and microglial area were marginally increased 24 h after MCH exposure. These results provide a foundation for further work investigating asthma-anxiety mechanisms.

House Dust Mite Exposure Causes Increased Susceptibility of Nasal Epithelial Cells to Adenovirus Infection

Adenovirus (AdV) infections in the respiratory tract may cause asthma exacerbation and allergic predisposition, and the house dust mite (HDM) may aggravate virus-induced asthma exacerbations. However, the underlying mechanisms of whether and how AdV affects asthmatic patients remains unclear. To address this question, we investigated nasal epithelial cells (NAEPCs) derived from a pediatric exacerbation study cohort for experimental analyses. We analyzed twenty-one different green-fluorescent protein- and luciferase-tagged AdV types in submerged 2D and organotypic 3D cell culture models. Transduction experiments revealed robust transduction of AdV type 5 (AdV5) in NAEPCs, which was associated with an increased uptake of AdV5 in the presence of HDM. In healthy and asthmatic NAEPCs exposed to HDM before infection, we observed a time- and dose-dependent increase of AdV5 uptake associated with upregulation of entry receptors for AdV5. Furthermore, electron microscopic and histologic analyses of 3D cell cultures revealed an impairment of the respiratory cilia after HDM exposition. This ex vivo pilot study shows the impact of AdV infection and HDM exposition in a primary cell culture model for asthma.

A new house dust mite-driven and mast cell-activated model of asthma in the guinea pig.

Animal models are extensively used to study underlying mechanisms in asthma. Guinea pigs share anatomical, pharmacological and physiological features with human airways and may enable the development of a pre-clinical in vivo model that closely resembles asthma. To develop an asthma model in guinea pigs using the allergen house dust mite (HDM). Guinea pigs were intranasally sensitized to HDM which was followed by HDM challenges once weekly for five weeks. Antigen-induced bronchoconstriction (AIB) was evaluated as alterations in Rn (Newtonian resistance), G (tissue damping) and H (tissue elastance) at the first challenge with forced oscillation technique (FOT), and changes in respiratory pattern upon each HDM challenge were assessed as enhanced pause (Penh) using whole-body plethysmography. Airway responsiveness to methacholine was measured one day after the last challenge by FOT. Inflammatory cells and cytokines were quantified in bronchoalveolar lavage fluid, and HDM-specific immunoglobulins were measured in serum by ELISA. Airway pathology was evaluated by conventional histology. The first HDM challenge after the sensitization generated a marked increase in Rn and G, which was abolished by pharmacological inhibition of histamine, leukotrienes and prostanoids. Repeated weekly challenges of HDM caused increase of Penh and a marked increase in airway hyperresponsiveness for all three lung parameters (Rn , G and H) and eosinophilia. Levels of IgE, IgG1 , IgG2 and IL-13 were elevated in HDM-treated guinea pigs. HDM exposure induced infiltration of inflammatory cells into the airways with a pronounced increase of mast cells. Subepithelial collagen deposition, airway wall thickness and goblet cell hyperplasia were induced by repeated HDM challenge. Repeated intranasal HDM administration induces mast cell activation and hyperplasia together with an asthma-like pathophysiology in guinea pigs. This model may be suitable for mechanistic investigations of asthma, including evaluation of the role of mast cells.

Organized lymphatic tissue (BALT) in lungs of rhesus monkeys after air pollutant exposure.

The presence of bronchus-associated lymphoid tissue (BALT) and its size in humans largely depends upon age. It is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. Environmental gases or allergens may have an effect on the number of BALT. Lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of BALT after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of house dust mite or a combination of ozone and house dust mite for 12 months. In the lungs of monkeys housed in filtered air for 2 months, no BALT was identified. After 6, 12, or 36 months, the number of BALT showed a significantly increased correlation with age in monkeys housed in filtered air. After 2 months of episodic house dust mite (HDM) exposure, no BALT was found. Monkeys exposed to HDM or HDM + ozone did not show a significant increase in BALT compared to monkeys housed in filtered air. However, monkeys exposed to ozone alone did show significant increases in BALT compared to all other groups. In particular, there were frequent accumulations of lymphocytes in the periarterial space of ozone exposed animals. In conclusion, BALT in rhesus monkeys housed under filtered air conditions is age-dependent. BALT significantly increased in monkeys exposed to ozone in comparison with monkeys exposed to HDM.

Tnfaip3 expression in pulmonary conventional type 1 Langerin-expressing dendritic cells regulates T helper 2-mediated airway inflammation in mice.

BackgroundConventional type 1 dendritic cells (cDC1s) control anti‐viral and anti‐tumor immunity by inducing antigen‐specific cytotoxic CD8+ T‐cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF‐κB, might determine the precise outcome of Th‐cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2‐driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF‐κB signaling.MethodsTo target pulmonary cDC1s, Cd207 (Langerin)‐mediated excision of A20/Tnfaip3 was used, generating Tnfaip3 fl/flxCd207 +/cre (Tnfaip3 Lg‐KO) mice. Mice were exposed to house dust mite (HDM) to provoke Th2‐mediated immune responses.ResultsMice harboring Tnfaip3‐deficient cDC1s did not develop Th2‐driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ‐expressing CD8+ T cells. In addition, Tnfaip3 Lg‐KO mice harbored increased numbers of IL‐12–expressing cDC1s and elevated PD‐L1 expression in all pulmonary DC subsets. Blocking either IL‐12 or IFNγ in Tnfaip3 Lg‐KO mice restored Th2 responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2 development.ConclusionsThese findings indicate that the activation status of cDC1s, shown by their specific expression of co‐inhibitory molecules and cytokines, critically contributes to the development of Th2 cell–mediated disorders, most likely by influencing IFNγ production in CD8+ T cells.

Cul5 E3 ubiquitin ligase limits Th2 and Th9 differentiation by regulating IL4 receptor level in CD4 T cells

Abstract Allergic asthma is a chronic airway disease characterized by increased airway resistance and airway remodeling. It is well established that increased Th2 and Th9 cells is responsible for this phenotype, the mechanisms restricting these cell numbers are poorly understood. Here we show that the E3 ubiquitin ligase, Cul5, restricts Th2 and Th9 differentiation and prevents allergic asthma. We found that Cul5 activity measured by neddylation is increased following CD4 T cell stimulation. We generated mice lacking Cul5 in T cells that showed mild Th2 inflammation in lung specifically. Upon house dust mite exposure these mice exhibited increased eosinophilia, goblet cell hyperplasia, and airways remodeling. Mechanistically, we show that in activated T cells, Cul5 associated with cytokine-induced SH2 protein (CIS), a SOCS-box protein. CIS act as a substrate receptor for Cul5 E3 ubiquitin complex and limits IL-4 receptor level on the surface, that correlated with increased Th2 and Th9 differentiation and/or persistence in vivo. These data support that Cul5 works with CIS to attenuate IL-4R signaling and reduce susceptibility to allergic asthma.

Sex Differences in Airway Inflammation and Structural Properties in a Mouse Model of House Dust Mite Challenge

BackgroundAsthma is a chronic airway disease that leads to compromised lung function and affects more than 300 million patients worldwide, leading to >180,000 deaths each year, many of which are avoidable with proper treatment and care. Despite significant advances in diagnostic and treatment of the disease, asthma continues to be a significant health problem and an economic burden. Epidemiological studies in adult populations have revealed sex differences in asthma morbidity, with higher incidence in females than males. The causes of this disparity are still unclear, but studies have shown that sex‐specific signaling pathways regulated by hormones contribute to differences in immune cell activation and airway reactivity in response to different environmental stimuli.MethodsWith the goal of understanding the mechanisms associated with the observed sex disparities in allergen‐induced asthma, we challenged both male and female adult C57BL/6J mice with a house dust mite (HDM) solution from two species, Dermatophagoides pteronyssinus and Dermatophagoides farinae. The protocol consisted of five consecutive intranasal challenges with 25μg of HDM or control (PBS) followed by two days off, repeated for five weeks. The asthma phenotype was assessed by testing airway hyperresponsiveness (AHR) to methacholine challenge, and airway inflammation was characterized by cell differential assessment of bronchoalveolar lavage fluid obtained from experimental animals. Lung tissue was harvested for inflammatory mRNA expression determinations and histology. Airway remodeling was characterized using the two‐photon imaging technique, second harmonic generation (SHG), on lung tissue sections to determine collagen content in mouse airways (Velocity, imaging quantification software).ResultsWe found that HDM promoted alterations in respiratory mechanics in challenged animals, including alterations in lung function measures that led to airway hyperresponsiveness (AHR) and increased parenchymal elastance in both males and females. While HDM‐challenged male mice showed higher AHR, airway collagen & elastin content, and BALF eosinophilia than females, challenged females displayed higher BALF neutrophilia and expression of type II pro‐inflammatory cytokines than males.ConclusionOur results indicate sex differences in both inflammatory and immune responses, as well as in airway structural changes induced by HDM exposure in mice. Characterization of the mechanisms leading to these sex differences will provide better insight into the causes of sex disparities observed in asthma prevalence and severity.Support or Funding InformationThis work was supported by NIH grants HL133520 (PS) and HL141618 (PS) and the APS Porter Fellowship (NF)

Diesel exhaust particle and dust mite induced airway inflammation is modified by cerium dioxide nanoparticles

Cerium dioxide nanoparticles (CeO2NPs) have been used as diesel fuel-borne catalysts for improved efficiency and pollutant emissions. Concerns that such material may influence diesel exhaust particle (DEP) effects within the lung upon inhalation, prompted us to examine particle responses in mice in the presence and absence of the common allergen house dust mite (HDM). Repeated intranasal instillation of combined HDM and DEP increased airway mucin, eosinophils, lymphocytes, IL-5, IL-13, IL-17A and plasma IgE, which were further increased with CeO2NPs co-exposure. A single co-exposure of CeO2NPs and DEP after repeated HDM exposure increased macrophage and IL-17A levels above DEP induced levels. CeO2NPs exposure in the absence of HDM also resulted in increased levels of plasma IgE and airway mucin staining, changes not observed with repeated DEP exposure alone. These observations indicate that CeO2NPs can modify exhaust particulate and allergen induced inflammatory events in the lung with the potential to influence conditions such as allergic airway disease.

Physiologic response to chronic house dust mite exposure in mice is dependent on lot characteristics

Physiologic response to chronic house dust mite exposure in mice is dependent on lot characteristics

Effects of Diatomaceous Earth on House Dust Mite Sensitization in BALB/c Mice

House Dust Mite (HDM) is associated with hypersensitivity such as asthma. Patients with asthma benefit from improved living environment by reducing HDM exposure. In this study, we examined the effects of commercialized diatomaceous earth product, Casaggia® used as construction materials, on hypersensitivity in HDM-sensitized mice. Male mice were sensitized with house dust mite extract for 7d and then housed in diatomaceous earth (DE)-coated cages for 14 days at Animal Center of the Taichung Veterans General Hospital, Taichung, Taiwan in 2014. Levels of cytokine were determined using ELISA. White blood cell counts were recorded over 21d. Histological analysis was conducted to determine the remodeling of respiratory tract. Exposure to DE resulted in a suppression in elevated eosinophilia induced by HDM in mice. In addition, elevated serum IgE responding to HDM sensitization were restored in the presence of DE. DE ameliorated the inflammation progression in airway. Environmental exposure to DE is suggested to benefit patients with hypersensitivity through relieving inflammatory symptoms. In a sense of prevention, DE represents a potential material against development of asthma.

A review of house dust mite allergy in India.

House dust mites (HDMs) are extensively reported as potent allergens worldwide with India being in the top row. HDM sensitization is hugely reported from India and has led to the concern of implementing proper guidelines for treatment of the sufferers. Climatic conditions and a rapid shift of life style toward a more indoor and urbanised pattern are denoted as the probable causes of increased HDM exposure and sensitization. On the contrary, the varying rate of HDM allergy from similar climate and urbanised areas throughout the world suggest the influence of genetic predisposition. At present, in India, avoidance of HDM exposure is recommended as the baseline defence. Allergen immunotherapy (AIT) guidelines are proposed in India to maintain uniformity in the diagnosis techniques and management strategies throughout the country. Considering the genetic susceptibility toward allergic diseases, the concept of 'personalised medicine' is preferred over the 'mass targeted treatment'. From the Indian perspective, the present problem is Dermatophagoides pteronyssinus and D. farinae allergens are not well characterised at the molecular level. As a consequence, India is still reliant on less standardised allergen extracts. The proper identification, purification, and molecular characterization of HDM allergens can combat this problem. In this review, we aimed to portray a complete account of HDM allergy in India with respect to prevalence, probable triggers, diagnosis and therapy. We have attempted to present the current ambiguities along with the likely deciphering that would pave the way to solve HDM allergy-related queries in India.

Age-dependent pulmonary reactivity to house dust mite allergen: a model of adult-onset asthma?

Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.

CD14 promotor polymorphisms associated with different allergic phenotypes and modulated with house dust mite allergy

Background: House dust mite (HDM) constitutes a major cause of allergic disease all over the world; meanwhile interaction between genetic control, environmental factors in the context of allergen exposure may affect allergic phenotype. Cluster of Differentiation 14 (CD14) polymorphisms play a major role in genetic control of allergic phenotype.Objective: We aimed to assess the role of CD14 genetic polymorphisms at two loci A(-1,145)G, and G(-1,359)T in expression of atopic asthma and allergic rhinitis in the context of HDM exposure in Jazan, KSA.Subjects and Methods: Through a case control study, 160 subjects served as 60 atopic asthmatic patients, 40 allergic rhinitis patients and 60 healthy non-allergic controls. Clinical and immunological parameters for the studied subjects were assessed. Then, genotyping of two single nucleotide polymorphisms (SNPs) at A(-1,145)G, and G(-1,359)T, in the promoter region of the CD14 gene was conducted using restriction fragment length polymorphisms (RFLP-PCR).Results: The present study showed that in HDM sensitive subjects there was a significant association between GG genotype variant at A(-1,145)G with atopic asthma patients and another significant association between TT genotype variant at G(-1,359)T with allergic rhinitis patients.Conclusion: The impact of allergy induced by HDMs may be enhanced in individuals with specific CD14 gene variants resulting in exaggerated allergic phenotype.

House dust mite exposure attenuates influenza A infection in a mouse model of pulmonary allergic inflammation

Environmental allergens elicit complex immune responses in the lungs that can promote the development of asthma or exacerbate preexisting asthma in susceptible individuals. House dust mites are one of the most common indoor allergens and are a significant driver of allergic disease. Respiratory infections are known factors in acute exacerbations of asthma but the impact of allergen on the pathogen is not well understood. We investigated the pathogenesis of influenza A infection following exposure to house dust mites. Mice exposed to house dust mites lose less weight following infection and had more transcription of interferon-lambda than controls. These data correlated with less transcription of the influenza polymerase acidic gene suggesting diminished viral replication in house dust mite exposed mice. Altogether, these data suggest that exposure to environmental allergens can influence the pathogenesis of influenza infection.

Quantum dots and mouse strain influence house dust mite-induced allergic airway disease

Quantum dot nanoparticles (QDs) are engineered nanomaterials (ENMs) that have utility in many industries due to unique optical properties not available in small molecules or bulk materials. QD-induced acute lung inflammation and toxicity in rodent models raise concerns about potential human health risks. Recent studies have also shown that some ENMs can exacerbate allergic airway disease (AAD).In this study, C57BL/6J and A/J mice were exposed to saline, house dust mite (HDM), or a combination of HDM and QDs on day 1 of the sensitization protocol. Mice were then challenged on days 8, 9 and 10 with HDM or saline only.Significant differences in cellular and molecular markers of AAD induced by both HDM and HDM + QD were observed between C57BL/6J and A/J mice. Among A/J mice, HDM + QD co-exposure, but not HDM exposure alone, significantly increased levels of bronchoalveolar lavage fluid (BALF). IL-33 compared to saline controls. BALF total protein levels in both mouse strains were also only significantly increased by HDM + QD co-exposure. In addition, A/J mice had significantly more lung type 2 innate lymphoid cells (ILC2s) cells than C57BL/6J mice. A/J lung ILC2s were inversely correlated with lung glutathione and MHC-IIhigh resident macrophages, and positively correlated with MHC-IIlow resident macrophages.The results from this study suggest that 1) QDs influence HDM-induced AAD by potentiating and/or enhancing select cytokine production; 2) that genetic background modulates the impact of QDs on HDM sensitization; and 3) that potential ILC2 contributions to HDM induced AAD are also likely to be modulated by genetic background.