Insights Into Mucosal Innate Immune Responses in House Dust Mite-Mediated Allergic Asthma

Abstract

The prevalence of asthma has been rising steadily for several decades, and continues to be a major public health and global economic burden due to both direct and indirect costs. Asthma is defined as chronic heterogeneous inflammatory diseases characterized by airway obstruction, mucus production and bronchospasm. Different endotypes of asthma are being recognized based on the distinct pathophysiology, genetic predisposition, age, prognosis, and response to remedies. Mucosal innate response to environmental triggers such as pollen, cigarette smoke, fragrances, viral infection, and house dust mite (HDM) are now recognized to play an important role in allergic asthma. HDM are the most pervasive allergens that co-habitat with us, as they are ubiquitous in-house dusts, mattress and bedsheets, and feed on a diet of exfoliated human skin flakes. Dermatophagoides pteronyssinus, is one among several HDM identified up to date. During the last decade, extensive studies have been fundamental in elucidating the interactions between HDM allergens, the host immune systems and airways. Moreover, the paradigm in the field of HDM-mediated allergy has been shifted away from being solely a Th2-geared to a complex response orchestrated via extensive crosstalk between the epithelium, professional antigen presenting cells (APCs) and components of the adaptive immunity. In fact, HDM have several lessons to teach us about their allergenicity, the complex interactions that stimulate innate immunity in initiating and perpetuating the lung inflammation. Herein, we review main allergens of Dermatophagoides pteronyssinus and their interactions with immunological sentinels that promote allergic sensitization and activation of innate immunity, which is critical for the development of the Th2 biased adaptive immunity to HDM allergens and development of allergic asthma.

Keywords: allergy; asthma; house dust mite; innate immunity; mucosal.

Figure 1

Overview of mucosal immune cells, molecules, and pathways targeted by house dust mite proteins to promote allergic asthma. The main allergen of house dust mite (HDM) is Der p 1, a cysteine protease. In addition to being an antigen, Der p 1 promotes allergic asthma through its action on a number of immune cells and molecules. Thus, Der p 1 can cleave tight junction proteins of epithelial cells and gain access to immune cells including naïve dendritic cells. It can also activate protease sensitive receptors (PARs) and TLR4, or promote cell injury in epithelial cells. This will result in the activation of NLRP3 inflammasome and secretion of cytokines and chemokines that recruit myeloid cells including dendritic cells, eosinophils, and ILC2. Cleavage of CD40 limits the production of IL-12 and IFNγ and thus, favors the polarization of Th2 cells. Der p 1 enhances the production of IgE though cleavage of CD23 receptor, which disrupts the negative feedback for regulation of IgE production. Finally, cross-linking of Der p 1-specific IgE on mast cells by Der p 1 mediates mast cell degranulation and release of histamine and other mediators associated with the symptoms of the allergic asthma.