Adjuvant-independent airway sensitization and infection mouse models leading to allergic asthma

Abstract

Asthma is a chronic respiratory disease of global importance. Mouse models of allergic asthma have been instrumental in advancing research and novel therapeutic strategies for patients. The application of relevant allergens and physiological routes of exposure in such models has led to valuable insights into the complexities of asthma onset and development as well as key disease mechanisms. Furthermore, environmental microbial exposures and infections have been shown to play a fundamental part in asthma pathogenesis and alter disease outcome. In this review, we delve into physiological mouse models of allergic asthma and explore literature reports on most significant interplays between microbial infections and asthma development with relevance to human disease.

Keywords: adjuvant-free; allergic asthma; microbial infection; mouse model; natural allergen; sensitization.

Figure 1

Hallmarks of allergic asthma. Asthma is a multifactorial disorder whose initial development seems influenced by predisposing factors, such as (epi)genetics, environmental exposures and lifestyle. The underlying cascade of immune events is often triggered and amplified by a misdirected immune response against apparently harmless environmental substances. Repeated allergen exposure of the airway then results in the clinical manifestations of the disease. On basis of these observations and in an attempt to simplify a highly complex pathology, we propose the following 8 hallmarks of allergic asthma. Predisposing hallmarks which encompass major risk factors [(1) genetic and epigenetic determinants, (2) environmental influences, such as pollution or microbes and (3) lifestyle factors, such as smoking, medication or dietary habits] that facilitate hallmarks of initiation [based on (4) misguided sensing of environmental substances as noxious, leading to (5) a dysregulated immune response], resulting in allergic sensitization. Finally, recurring airway allergen exposure results in manifestation hallmarks of allergic asthma, consist of major clinical and pathological characteristics [(6) chronic lung inflammation, (7) airway remodeling, and (8) impaired lung function]. This illustration was created with BioRender.com.

Figure 2

Modelling allergic asthma: mouse vs human. Mouse models of allergic asthma response ideally implement fundamental principles that consider physiologic aspects related to disease onset and progression in humans. As such, mouse models should consider physiologic allergen exposure conditions via barrier organs, utilize relevant allergens and avoid clinically irrelevant adjuvants, as well as incorporate realistic protocols of allergen exposure. This illustration was created with BioRender.com.