Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

Abstract

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed.

Figure 1

Schematic presentation of how the effects of environmental exposures, (aero)immunization and airway challenge on the 3 different phases of the asthma pathology (sensitization, acute inflammation and chronic disease) can be dissected in mice.

Figure 2

Diesel exhaust particles (DEP) and cigarette smoke affect allergic sensitization and the development or exacerbation of asthma. Similar proposed mechanisms for both inhalable pollutants, obtained from human, mouse and in vitro data are shown. Both DEP and cigarette smoke induce tissue damage and oxidative stress, resulting in a pulmonary inflammation with increased neutrophils and T-cells, and increased pro-inflammatory cytokines. This creates an environment which facilitates allergic sensitization. Cell types and mediators that are increased upon the combination of allergen and inhalable pollutant exposure (both DEP and cigarette smoke) and which are specifically associated with allergic asthma are indicated with a small black arrow.