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

ABSTRACT: 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.

SUBMITTER: Hu Q

PROVIDER: S-EPMC7336117 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Hu Qiyao Q Gilley Ryan P RP Dube Peter H PH

Microbial pathogenesis 20190215

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 exposur ...[more]

PMID: 30776411

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Frontline Science: RIP2 promotes house dust mite-induced allergic airway inflammation.

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| S-EPMC6113092 | biostudies-literature

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

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IL-22 inhibits allergic airway inflammation in house dust mite-induced asthma models

Project description:While the pathogenesis of asthma is mainly orchestrated by antigen-specific Th2 cells and their cytokines, recent findings indicate the involvement of other subsets of helper T cells including Th17 cells. Previous studies have shown that IL-22, one of Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation; however, the mechanism underlying the Il-22-mediated regulation remains unclear. Here, we show that allergic airway inflammation upon intratracheal administration of house dust mite extract (HDM), a representative allergen, were exacerbated in IL-22-deficient mice. To address the molecular mechanisms by which IL-22 inhibits the development of HDM-induced allergic airway inflammation, we next performed an unbiased comprehensive screening of genes induced by IL-22 administration in the lung by RNA-seq analysis.

2017-08-10 | GSE100858 | GEO

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.

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Project description:Regulation of epithelial cell death has emerged as a key mechanism controlling immune homeostasis in barrier surfaces. Necroptosis is a type of regulated necrotic cell death induced by receptor interacting protein kinase 3 (RIPK3) that has been shown to cause inflammatory pathologies in different tissues. The role of regulated cell death and particularly necroptosis in lung homeostasis and disease remains poorly understood. Here we show that mice with Airway Epithelial Cell (AEC)-specific deficiency of Fas-associated with death domain (FADD), an adapter essential for caspase-8 activation, developed exacerbated allergic airway inflammation in a mouse model of asthma induced by sensitization and challenge with house dust mite (HDM) extracts. Genetic inhibition of RIPK1 kinase activity by crossing to mice expressing kinase inactive RIPK1 as well as RIPK3 or MLKL deficiency prevented the development of exaggerated HDM-induced asthma pathology in FADDAEC-KO mice, suggesting that necroptosis of FADD-deficient AECs augmented the allergic immune response. These results reveal a role of AEC necroptosis in amplifying airway allergic inflammation and suggest that necroptosis could contribute to asthma exacerbations caused by respiratory virus infections inducing AEC death.

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IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models.

Project description:Previous studies have shown that IL-22, one of the Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway inflammation and Th2 and Th17 cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative allergen, were exacerbated in IL-22-deficient mice. We also found that IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway inflammation and Th2 cytokine induction. Moreover, exostatin-like 3 (EXTL3), a functional Reg3γ binding protein, is expressed in lung epithelial cells, and intratracheal administration of recombinant Reg3γ suppresses HDM-induced thymic stromal lymphopoietin and IL-33 expression and accumulation of type 2 innate lymphoid cells in the lung. Collectively, these results suggest that IL-22 induces Reg3γ production from lung epithelial cells and inhibits the development of HDM-induced allergic airway inflammation, possibly by inhibiting cytokine production from lung epithelial cells.

| S-EPMC5626396 | 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

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